chr17-28395626-G-A

Variant names:

• chr17-28395626-G-A
• rs8079943
• NM_080669.6:c.*4030C>T

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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.746
• Publications: 8 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=-0.91).
• BP6: Variant 17-28395626-G-A is Benign according to our data. Variant chr17-28395626-G-A is described in ClinVar as Benign. ClinVar VariationId 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.

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.*4030C>T		3_prime_UTR	Exon 5 of 5	NP_542400.2
	SARM1	NM_015077.4	MANE Select	c.1924-279G>A		intron	N/A	NP_055892.2	Q6SZW1-1
	SLC46A1	NM_001242366.3		c.*4030C>T		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.*4030C>T		3_prime_UTR	Exon 5 of 5	ENSP00000480703.1	Q96NT5-1
	SARM1	ENST00000585482.6	TSL:1 MANE Select	c.1924-279G>A		intron	N/A	ENSP00000468032.2	Q6SZW1-1
	SARM1	ENST00000886313.1		c.1924-279G>A		intron	N/A	ENSP00000556372.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 89892 AN: 151342 Hom.: 27040 Cov.: 32

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.: 2 AF XY: 0.562 AC XY: 61455 AN XY: 109330

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

GnomAD4 genome AF: 0.594 AC: 89944 AN: 151452 Hom.: 27050 Cov.: 32 AF XY: 0.588 AC XY: 43557 AN XY: 74030

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

Alfa AF: 0.492 Hom.: 2778

Bravo AF: 0.614

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	-0.91
CADD	Benign	1.2
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)

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: rs8079943; hg19: chr17-26722645;