chr17-28395709-C-T

Variant names:

• chr17-28395709-C-T
• rs8081240
• NM_080669.6:c.*3947G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0510
• Publications: 7 publications found

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]

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]

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080669.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC46A1	NM_080669.6	MANE Select	c.*3947G>A		3_prime_UTR	Exon 5 of 5	NP_542400.2
	SARM1	NM_015077.4	MANE Select	c.1924-196C>T		intron	N/A	NP_055892.2	Q6SZW1-1
	SLC46A1	NM_001242366.3		c.*3947G>A		3_prime_UTR	Exon 4 of 4	NP_001229295.1	Q96NT5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC46A1	ENST00000612814.5	TSL:2 MANE Select	c.*3947G>A		3_prime_UTR	Exon 5 of 5	ENSP00000480703.1	Q96NT5-1
	SLC46A1	ENST00000618626.1	TSL:1	c.*3947G>A		3_prime_UTR	Exon 4 of 4	ENSP00000483652.1	Q96NT5-2
	SARM1	ENST00000585482.6	TSL:1 MANE Select	c.1924-196C>T		intron	N/A	ENSP00000468032.2	Q6SZW1-1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89672 AN: 151892 Hom.: 26908 Cov.: 31

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.: 5 AF XY: 0.566 AC XY: 128351 AN XY: 226822

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

GnomAD4 genome AF: 0.590 AC: 89724 AN: 152010 Hom.: 26918 Cov.: 31 AF XY: 0.585 AC XY: 43461 AN XY: 74282

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

Alfa AF: 0.558 Hom.: 4706

Bravo AF: 0.612

Asia WGS AF: 0.555 AC: 1933 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital defect of folate absorption (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.76
PhyloP100		-0.051
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8081240; hg19: chr17-26722728;