chr17-28392769-G-A

Position:

• chr17-28392769-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SARM1	NM_015077.4	c.1924-3136G>A		intron_variant		ENST00000585482.6	NP_055892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SARM1	ENST00000585482.6	c.1924-3136G>A		intron_variant		1	NM_015077.4	ENSP00000468032	P1

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

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.0381

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.138

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs35714695; hg19: chr17-26719788;