4-164768514-T-C

Variant names:

• chr4-164768514-T-C
• rs7659335
• NM_001352885.1:c.-25-1905T>C

Variant summary

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

The NM_001352885.1(SMIM31):​c.-25-1905T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,036 control chromosomes in the GnomAD database, including 18,200 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 0.48 (18200 hom., cov: 29)
• Consequence: SMIM31 NM_001352885.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 1 publications found

Genes affected

SMIM31 (HGNC:49638): (small integral membrane protein 31) Predicted to be located in axon. [provided by Alliance of Genome Resources, Apr 2022]

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 (AMR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMIM31	NM_001352885.1	c.-25-1905T>C		intron_variant	Intron 1 of 2	ENST00000507311.1	NP_001339814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMIM31	ENST00000507311.1	c.-25-1905T>C		intron_variant	Intron 1 of 2	1	NM_001352885.1	ENSP00000490699.1
SMIM31	ENST00000515485.5	c.-25-1905T>C		intron_variant	Intron 2 of 3	5		ENSP00000493952.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72141 AN: 150930 Hom.: 18181 Cov.: 29

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.478 AC: 72169 AN: 151036 Hom.: 18200 Cov.: 29 AF XY: 0.474 AC XY: 34942 AN XY: 73686

African (AFR) AF: 0.323 AC: 13272 AN: 41130

American (AMR) AF: 0.565 AC: 8539 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1617 AN: 3466

East Asian (EAS) AF: 0.449 AC: 2290 AN: 5104

South Asian (SAS) AF: 0.430 AC: 2047 AN: 4766

European-Finnish (FIN) AF: 0.478 AC: 4931 AN: 10320

Middle Eastern (MID) AF: 0.403 AC: 116 AN: 288

European-Non Finnish (NFE) AF: 0.560 AC: 38020 AN: 67850

Other (OTH) AF: 0.449 AC: 941 AN: 2098

Alfa AF: 0.514 Hom.: 2550

Bravo AF: 0.480

Asia WGS AF: 0.446 AC: 1551 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	3.6
DANN	Benign	0.73
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs7659335; hg19: chr4-165689666;