rs2239907

Variant names:

• chr17-28398728-T-C
• rs2239907
• NM_015077.4:c.*2442T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-28398728-T-C
• chr17-28398728-T-A
• chr17-28398728-T-G

Variant summary

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

The NM_015077.4(SARM1):​c.*2442T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,180 control chromosomes in the GnomAD database, including 22,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22239 hom., cov: 33)
  • Exomes 𝑓: 0.60 (20 hom.)
• Consequence: SARM1 NM_015077.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.891
• Publications: 27 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• hereditary folate malabsorption

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-28398728-T-C is Benign according to our data. Variant chr17-28398728-T-C is described in ClinVar as Benign. ClinVar VariationId is 322393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015077.4. 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
	SARM1	NM_015077.4	MANE Select	c.*2442T>C		3_prime_UTR	Exon 9 of 9	NP_055892.2	Q6SZW1-1
	SLC46A1	NM_080669.6	MANE Select	c.*928A>G		3_prime_UTR	Exon 5 of 5	NP_542400.2
	SLC46A1	NM_001242366.3		c.*928A>G		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
	SARM1	ENST00000585482.6	TSL:1 MANE Select	c.*2442T>C		3_prime_UTR	Exon 9 of 9	ENSP00000468032.2	Q6SZW1-1
	SLC46A1	ENST00000612814.5	TSL:2 MANE Select	c.*928A>G		3_prime_UTR	Exon 5 of 5	ENSP00000480703.1	Q96NT5-1
	SLC46A1	ENST00000618626.1	TSL:1	c.*928A>G		3_prime_UTR	Exon 4 of 4	ENSP00000483652.1	Q96NT5-2

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81636 AN: 151966 Hom.: 22249 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.604 AC: 58 AN: 96 Hom.: 20 Cov.: 0 AF XY: 0.611 AC XY: 44 AN XY: 72

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.635 AC: 47 AN: 74

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.537 AC: 81653 AN: 152084 Hom.: 22239 Cov.: 33 AF XY: 0.533 AC XY: 39606 AN XY: 74348

African (AFR) AF: 0.475 AC: 19700 AN: 41446

American (AMR) AF: 0.613 AC: 9369 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1965 AN: 3472

East Asian (EAS) AF: 0.727 AC: 3768 AN: 5184

South Asian (SAS) AF: 0.535 AC: 2577 AN: 4820

European-Finnish (FIN) AF: 0.434 AC: 4589 AN: 10570

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37771 AN: 67988

Other (OTH) AF: 0.579 AC: 1220 AN: 2108

Alfa AF: 0.561 Hom.: 22789

Bravo AF: 0.551

Asia WGS AF: 0.556 AC: 1934 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	-0.82
CADD	Benign	5.2
DANN	Benign	0.73
PhyloP100		0.89
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: rs2239907; hg19: chr17-26725744;