NM_015077.4:c.1924-3136G>A

Variant names:

• chr17-28392769-G-A
• rs35714695
• NM_015077.4:c.1924-3136G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_015077.4(SARM1):​c.1924-3136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,182 control chromosomes in the GnomAD database, including 1,452 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1452 hom., cov: 32)
• Consequence: SARM1 NM_015077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 10 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARM1	NM_015077.4	c.1924-3136G>A		intron_variant	Intron 7 of 8	ENST00000585482.6	NP_055892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARM1	ENST00000585482.6	c.1924-3136G>A		intron_variant	Intron 7 of 8	1	NM_015077.4	ENSP00000468032.2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19098 AN: 152064 Hom.: 1451 Cov.: 32

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.125 AC: 19098 AN: 152182 Hom.: 1452 Cov.: 32 AF XY: 0.125 AC XY: 9266 AN XY: 74398

African (AFR) AF: 0.0472 AC: 1959 AN: 41542

American (AMR) AF: 0.111 AC: 1698 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3468

East Asian (EAS) AF: 0.0381 AC: 197 AN: 5174

South Asian (SAS) AF: 0.179 AC: 864 AN: 4820

European-Finnish (FIN) AF: 0.132 AC: 1401 AN: 10580

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11690 AN: 67988

Other (OTH) AF: 0.138 AC: 292 AN: 2110

Alfa AF: 0.0680 Hom.: 74

Bravo AF: 0.120

Asia WGS AF: 0.123 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.4
DANN	Benign	0.79
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: -4

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

Other links and lift over

dbSNP: rs35714695; hg19: chr17-26719788;