rs5996091

Variant names:

• chr22-41948262-A-G
• rs5996091
• NM_001395946.1:c.-15+956A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_001395946.1(SMIM45):​c.-15+956A>G variant causes a intron 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 NM_001395946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMIM45	NM_001395946.1	c.-15+956A>G		intron_variant	Intron 1 of 1		NP_001382875.1
SMIM45	NM_001395947.1	c.-15+454A>G		intron_variant	Intron 1 of 1		NP_001382876.1
SMIM45	NM_001395948.1	c.-152+956A>G		intron_variant	Intron 1 of 2		NP_001382877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMIM45	ENST00000711329.1	c.-15+956A>G		intron_variant	Intron 1 of 1			ENSP00000518693.1

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

African (AFR) AF: 0.292 AC: 12118 AN: 41466

American (AMR) AF: 0.315 AC: 4803 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3468

East Asian (EAS) AF: 0.0466 AC: 241 AN: 5172

South Asian (SAS) AF: 0.186 AC: 895 AN: 4816

European-Finnish (FIN) AF: 0.110 AC: 1171 AN: 10604

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7835 AN: 68006

Other (OTH) AF: 0.177 AC: 374 AN: 2114

Alfa AF: 0.140 Hom.: 944

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
PhyloP100		0.75

Splicing

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

Other links and lift over

dbSNP: rs5996091; hg19: chr22-42344266;