rs5996091

Positions:

• chr22-41948262-A-G
• chr22-41948262-A-T

Variant summary

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

The NR_172941.1(SMIM45):​n.358+956A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,120 control chromosomes in the GnomAD database, including 3,355 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 0.19 (3355 hom., cov: 31)
• Consequence: SMIM45 NR_172941.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753

Genes affected

SMIM45 (HGNC:27930): (small integral membrane protein 45) 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMIM45	NR_172941.1	n.358+956A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM45	ENST00000711329.1	c.-15+956A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28191 AN: 152002 Hom.: 3338 Cov.: 31

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0475

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.186 AC: 28251 AN: 152120 Hom.: 3355 Cov.: 31 AF XY: 0.187 AC XY: 13913 AN XY: 74376

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0466

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.177

Alfa AF: 0.140 Hom.: 856

Bravo AF: 0.212

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5996091; hg19: chr22-42344266;