rs8140869

Variant names:

• chr22-41948293-G-A
• rs8140869
• NM_001395946.1:c.-15+987G>A

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+987G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,026 control chromosomes in the GnomAD database, including 4,529 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 (4529 hom., cov: 31)
• Consequence: SMIM45 NM_001395946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 16 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMIM45	NM_001395946.1	c.-15+987G>A		intron_variant	Intron 1 of 1		NP_001382875.1
SMIM45	NM_001395947.1	c.-15+485G>A		intron_variant	Intron 1 of 1		NP_001382876.1
SMIM45	NM_001395948.1	c.-152+987G>A		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+987G>A		intron_variant	Intron 1 of 1			ENSP00000518693.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35418 AN: 151908 Hom.: 4522 Cov.: 31

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.233 AC: 35440 AN: 152026 Hom.: 4529 Cov.: 31 AF XY: 0.226 AC XY: 16763 AN XY: 74302

African (AFR) AF: 0.309 AC: 12796 AN: 41440

American (AMR) AF: 0.156 AC: 2385 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3470

East Asian (EAS) AF: 0.00348 AC: 18 AN: 5168

South Asian (SAS) AF: 0.143 AC: 690 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2082 AN: 10566

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15815 AN: 67968

Other (OTH) AF: 0.213 AC: 451 AN: 2116

Alfa AF: 0.232 Hom.: 10058

Bravo AF: 0.230

Asia WGS AF: 0.0970 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs8140869; hg19: chr22-42344297;