rs4471745

chr17-55491523-G-A

Variant summary

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

The NM_001395421.2(SMIM36):c.*175-11943C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 152,082 control chromosomes in the GnomAD database, including 367 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 0.065 (367 hom., cov: 31)
• Consequence: SMIM36 NM_001395421.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

SMIM36 (HGNC:53654): (small integral membrane protein 36) 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMIM36	NM_001395421.2	c.*175-11943C>T		intron_variant		ENST00000636752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM36	ENST00000636752.2	c.*175-11943C>T		intron_variant		5	NM_001395421.2	P1
SMIM36	ENST00000577089.1	n.61-12710C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0649 AC: 9857 AN: 151964 Hom.: 351 Cov.: 31

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0411

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0970

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0651 AC: 9896 AN: 152082 Hom.: 367 Cov.: 31 AF XY: 0.0629 AC XY: 4679 AN XY: 74330

Gnomad4 AFR AF: 0.0652

Gnomad4 AMR AF: 0.0410

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.0981

Gnomad4 FIN AF: 0.0473

Gnomad4 NFE AF: 0.0690

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0647 Hom.: 468

Bravo AF: 0.0627

Asia WGS AF: 0.160 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.2
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4471745; hg19: chr17-53568884;