rs4936417

chr11-118033121-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394165.1(SMIM35):c.8-17312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,168 control chromosomes in the GnomAD database, including 4,717 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 0.23 (4717 hom., cov: 32)
• Consequence: SMIM35 NM_001394165.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

Genes affected

SMIM35 (HGNC:44179): (small integral membrane protein 35) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMIM35	NM_001394165.1	c.8-17312A>G		intron_variant		ENST00000689828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM35	ENST00000689828.1	c.8-17312A>G		intron_variant			NM_001394165.1	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34943 AN: 152050 Hom.: 4714 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.230 AC: 34962 AN: 152168 Hom.: 4717 Cov.: 32 AF XY: 0.223 AC XY: 16559 AN XY: 74372

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.0600

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.222

Alfa AF: 0.288 Hom.: 13576

Bravo AF: 0.219

Asia WGS AF: 0.111 AC: 386 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	6.4
Dann	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4936417; hg19: chr11-117903836;