chr22-41948404-A-G

Variant names:

• chr22-41948404-A-G
• rs5996092
• NM_001395946.1:c.-15+1098A>G

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+1098A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,976 control chromosomes in the GnomAD database, including 28,151 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 0.57 (28151 hom., cov: 31)
• Consequence: SMIM45 NM_001395946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395946.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM45	NM_001395946.1		c.-15+1098A>G		intron	N/A	NP_001382875.1	A0A590UK83
	SMIM45	NM_001395947.1		c.-15+596A>G		intron	N/A	NP_001382876.1	A0A590UK83
	SMIM45	NM_001395948.1		c.-152+1098A>G		intron	N/A	NP_001382877.1	A0A590UK83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM45	ENST00000711329.1		c.-15+1098A>G		intron	N/A	ENSP00000518693.1	A0A590UK83
	SMIM45	ENST00000884376.1		c.-152+1098A>G		intron	N/A	ENSP00000554435.1
	SMIM45	ENST00000884377.1		c.-15+446A>G		intron	N/A	ENSP00000554436.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86766 AN: 151856 Hom.: 28081 Cov.: 31

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.572 AC: 86893 AN: 151976 Hom.: 28151 Cov.: 31 AF XY: 0.565 AC XY: 41979 AN XY: 74284

African (AFR) AF: 0.867 AC: 35949 AN: 41476

American (AMR) AF: 0.639 AC: 9736 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1848 AN: 3472

East Asian (EAS) AF: 0.135 AC: 696 AN: 5172

South Asian (SAS) AF: 0.481 AC: 2314 AN: 4808

European-Finnish (FIN) AF: 0.391 AC: 4131 AN: 10560

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30552 AN: 67934

Other (OTH) AF: 0.532 AC: 1122 AN: 2110

Alfa AF: 0.496 Hom.: 6957

Bravo AF: 0.604

Asia WGS AF: 0.369 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.98
DANN	Benign	0.67
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs5996092; hg19: chr22-42344408;