chr17-28395626-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080669.6(SLC46A1):c.*4030C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 359,870 control chromosomes in the GnomAD database, including 61,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27050 hom., cov: 32)

Exomes 𝑓: 0.56 ( 34148 hom. )

Consequence

SLC46A1
NM_080669.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.746

Publications

8 publications found

Variant links:

Genes affected

SLC46A1 (HGNC:30521): (solute carrier family 46 member 1) This gene encodes a transmembrane proton-coupled folate transporter protein that facilitates the movement of folate and antifolate substrates across cell membranes, optimally in acidic pH environments. This protein is also expressed in the brain and choroid plexus where it transports folates into the central nervous system. This protein further functions as a heme transporter in duodenal enterocytes, and potentially in other tissues like liver and kidney. Its localization to the apical membrane or cytoplasm of intestinal cells is modulated by dietary iron levels. Mutations in this gene are associated with autosomal recessive hereditary folate malabsorption disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2013]

SLC46A1 links:

SARM1 (HGNC:17074): (sterile alpha and TIR motif containing 1) Enables NAD+ nucleotidase, cyclic ADP-ribose generating and identical protein binding activity. Involved in NAD catabolic process; positive regulation of neuron death; and response to axon injury. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SARM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-28395626-G-A is Benign according to our data. Variant chr17-28395626-G-A is described in ClinVar as [Benign]. Clinvar id is 322346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC46A1	NM_080669.6 link	c.*4030C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000612814.5	NP_542400.2	Q96NT5-1A0A024QZ15
SARM1	NM_015077.4 link	c.1924-279G>A		intron_variant	Intron 7 of 8	ENST00000585482.6	NP_055892.2	Q6SZW1-1Q05B42Q0D2N8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC46A1	ENST00000612814.5 link	c.*4030C>T		3_prime_UTR_variant	Exon 5 of 5	2	NM_080669.6	ENSP00000480703.1		Q96NT5-1
SARM1	ENST00000585482.6 link	c.1924-279G>A		intron_variant	Intron 7 of 8	1	NM_015077.4	ENSP00000468032.2		Q6SZW1-1

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

89892

AN:

151342

Hom.:

27040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.678

Gnomad AMI

AF:

0.549

Gnomad AMR

AF:

0.630

Gnomad ASJ

AF:

0.566

Gnomad EAS

AF:

0.739

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.621

GnomAD4 exome

AF:

0.564

AC:

117533

AN:

208418

Hom.:

34148

Cov.:

AF XY:

0.562

AC XY:

61455

AN XY:

109330

show subpopulations

African (AFR)

AF:

0.679

AC:

4735

AN:

6972

American (AMR)

AF:

0.618

AC:

5832

AN:

9438

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

3532

AN:

6474

East Asian (EAS)

AF:

0.759

AC:

9533

AN:

12564

South Asian (SAS)

AF:

0.527

AC:

12744

AN:

24200

European-Finnish (FIN)

AF:

0.448

AC:

4519

AN:

10092

Middle Eastern (MID)

AF:

0.625

AC:

574

AN:

918

European-Non Finnish (NFE)

AF:

0.550

AC:

69223

AN:

125828

Other (OTH)

AF:

0.573

AC:

6841

AN:

11932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2400

4800

7200

9600

12000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.594

AC:

89944

AN:

151452

Hom.:

27050

Cov.:

AF XY:

0.588

AC XY:

43557

AN XY:

74030

show subpopulations

African (AFR)

AF:

0.677

AC:

27762

AN:

40978

American (AMR)

AF:

0.630

AC:

9620

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

1961

AN:

3466

East Asian (EAS)

AF:

0.740

AC:

3813

AN:

5154

South Asian (SAS)

AF:

0.523

AC:

2516

AN:

4814

European-Finnish (FIN)

AF:

0.434

AC:

4577

AN:

10538

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.555

AC:

37707

AN:

67942

Other (OTH)

AF:

0.617

AC:

1290

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1866

3733

5599

7466

9332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.492

Hom.:

2778

Bravo

AF:

0.614

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital defect of folate absorption

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

(source)

DANN

Benign

0.13

PhyloP100

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr17-28395626-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over