17-28379927-G-T

Variant names:

• chr17-28379927-G-T
• rs2027993
• NM_015077.4:c.471-1276G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015077.4(SARM1):​c.471-1276G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,944 control chromosomes in the GnomAD database, including 20,175 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 0.51 (20175 hom., cov: 32)
• Consequence: SARM1 NM_015077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 20 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]

ENSG00000258924 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARM1	NM_015077.4	c.471-1276G>T		intron_variant	Intron 1 of 8	ENST00000585482.6	NP_055892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARM1	ENST00000585482.6	c.471-1276G>T		intron_variant	Intron 1 of 8	1	NM_015077.4	ENSP00000468032.2
SARM1	ENST00000379061.8	n.171-1276G>T		intron_variant	Intron 2 of 10	2
ENSG00000258924	ENST00000591482.1	n.556-1276G>T		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77820 AN: 151826 Hom.: 20185 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.512 AC: 77830 AN: 151944 Hom.: 20175 Cov.: 32 AF XY: 0.509 AC XY: 37785 AN XY: 74250

African (AFR) AF: 0.459 AC: 19008 AN: 41446

American (AMR) AF: 0.584 AC: 8915 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1949 AN: 3460

East Asian (EAS) AF: 0.724 AC: 3745 AN: 5174

South Asian (SAS) AF: 0.502 AC: 2423 AN: 4822

European-Finnish (FIN) AF: 0.423 AC: 4456 AN: 10526

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35524 AN: 67938

Other (OTH) AF: 0.546 AC: 1153 AN: 2110

Alfa AF: 0.522 Hom.: 32007

Bravo AF: 0.526

Asia WGS AF: 0.537 AC: 1867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.68
PhyloP100		-0.85
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: rs2027993; hg19: chr17-26706946;