rs1175550

Positions:

• chr1-3774964-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMIM1	NM_001288583.2	c.-75-335A>G		intron_variant		ENST00000642557.4	NP_001275512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMIM1	ENST00000642557.4	c.-75-335A>G		intron_variant			NM_001288583.2	ENSP00000496314.2
SMIM1	ENST00000444870.7	c.-75-335A>G		intron_variant		1		ENSP00000457386.1
SMIM1	ENST00000561886.2	c.-75-335A>G		intron_variant		2		ENSP00000456559.1
SMIM1	ENST00000452264.1	c.-75-335A>G		intron_variant		2		ENSP00000457674.1

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

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.00255

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.269

Alfa AF: 0.261 Hom.: 1533

Bravo AF: 0.303

Asia WGS AF: 0.116 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs1175550; hg19: chr1-3691528;