1-3774964-A-G

Variant names:

• chr1-3774964-A-G
• rs1175550
• NM_001288583.2:c.-75-335A>G

Variant summary

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

The NM_001288583.2(SMIM1):​c.-75-335A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,530 control chromosomes in the GnomAD database, including 8,703 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 0.30 (8703 hom., cov: 31)
• Consequence: SMIM1 NM_001288583.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55
• Publications: 60 publications found

Genes affected

SMIM1 (HGNC:44204): (small integral membrane protein 1 (Vel blood group)) This gene encodes a small, conserved protein that participates in red blood cell formation. The encoded protein is localized to the cell membrane and is the antigen for the Vel blood group. Alternative splicing results in different transcript variants that encode the same protein. [provided by RefSeq, Dec 2013]

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 = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288583.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM1	NM_001288583.2	MANE Select	c.-75-335A>G		intron	N/A	NP_001275512.1
	SMIM1	NM_001163724.3		c.-75-335A>G		intron	N/A	NP_001157196.1
	SMIM1	NM_001379690.1		c.-75-335A>G		intron	N/A	NP_001366619.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM1	ENST00000642557.4	MANE Select	c.-75-335A>G		intron	N/A	ENSP00000496314.2
	SMIM1	ENST00000444870.7	TSL:1	c.-75-335A>G		intron	N/A	ENSP00000457386.1
	SMIM1	ENST00000561886.2	TSL:2	c.-75-335A>G		intron	N/A	ENSP00000456559.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 45966 AN: 151412 Hom.: 8681 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.00254

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.304 AC: 46046 AN: 151530 Hom.: 8703 Cov.: 31 AF XY: 0.300 AC XY: 22219 AN XY: 74014

African (AFR) AF: 0.524 AC: 21652 AN: 41328

American (AMR) AF: 0.183 AC: 2786 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3466

East Asian (EAS) AF: 0.00255 AC: 13 AN: 5106

South Asian (SAS) AF: 0.171 AC: 823 AN: 4802

European-Finnish (FIN) AF: 0.301 AC: 3155 AN: 10482

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15860 AN: 67784

Other (OTH) AF: 0.269 AC: 564 AN: 2100

Alfa AF: 0.270 Hom.: 1828

Bravo AF: 0.303

Asia WGS AF: 0.116 AC: 406 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	1.2
DANN	Benign	0.50
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1175550; hg19: chr1-3691528;