17-28395709-C-T

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.*3947G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 585,312 control chromosomes in the GnomAD database, including 98,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26918 hom., cov: 31)

Exomes 𝑓: 0.57 ( 71283 hom. )

Consequence

SLC46A1
NM_080669.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0510

Publications

7 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=-0.8).

BP6

Variant 17-28395709-C-T is Benign according to our data. Variant chr17-28395709-C-T is described in ClinVar as [Benign]. Clinvar id is 322348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC46A1	NM_080669.6 link	c.*3947G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000612814.5	NP_542400.2	Q96NT5-1A0A024QZ15
SARM1	NM_015077.4 link	c.1924-196C>T		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.*3947G>A		3_prime_UTR_variant	Exon 5 of 5	2	NM_080669.6	ENSP00000480703.1		Q96NT5-1
SARM1	ENST00000585482.6 link	c.1924-196C>T		intron_variant	Intron 7 of 8	1	NM_015077.4	ENSP00000468032.2		Q6SZW1-1

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89672

AN:

151892

Hom.:

26908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.667

Gnomad AMI

AF:

0.549

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.722

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.618

GnomAD4 exome

AF:

0.568

AC:

246180

AN:

433302

Hom.:

71283

Cov.:

AF XY:

0.566

AC XY:

128351

AN XY:

226822

show subpopulations

African (AFR)

AF:

0.671

AC:

8106

AN:

12074

American (AMR)

AF:

0.621

AC:

11191

AN:

18018

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

7268

AN:

13054

East Asian (EAS)

AF:

0.752

AC:

21846

AN:

29056

South Asian (SAS)

AF:

0.531

AC:

23094

AN:

43514

European-Finnish (FIN)

AF:

0.454

AC:

11976

AN:

26406

Middle Eastern (MID)

AF:

0.639

AC:

1183

AN:

1850

European-Non Finnish (NFE)

AF:

0.556

AC:

147170

AN:

264660

Other (OTH)

AF:

0.582

AC:

14346

AN:

24670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

5001

10002

15003

20004

25005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.590

AC:

89724

AN:

152010

Hom.:

26918

Cov.:

AF XY:

0.585

AC XY:

43461

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.667

AC:

27633

AN:

41444

American (AMR)

AF:

0.629

AC:

9613

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1963

AN:

3472

East Asian (EAS)

AF:

0.722

AC:

3720

AN:

5152

South Asian (SAS)

AF:

0.523

AC:

2519

AN:

4818

European-Finnish (FIN)

AF:

0.434

AC:

4580

AN:

10562

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.555

AC:

37705

AN:

67954

Other (OTH)

AF:

0.613

AC:

1292

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1899

3797

5696

7594

9493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.558

Hom.:

4706

Bravo

AF:

0.612

Asia WGS

AF:

0.555

AC:

1933

AN:

3478

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

-0.80

CADD

Benign

5.8

(source)

DANN

Benign

0.76

PhyloP100

-0.051

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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17-28395709-C-T

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