rs1175549

Positions:

• chr1-3775163-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288583.2(SMIM1):​c.-75-136A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 478,082 control chromosomes in the GnomAD database, including 18,633 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 0.31 (8975 hom., cov: 31)
  • Exomes 𝑓: 0.22 (9658 hom.)
• Consequence: SMIM1 NM_001288583.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMIM1	NM_001288583.2	c.-75-136A>C		intron_variant		ENST00000642557.4	NP_001275512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMIM1	ENST00000642557.4	c.-75-136A>C		intron_variant			NM_001288583.2	ENSP00000496314.2
SMIM1	ENST00000444870.7	c.-75-136A>C		intron_variant		1		ENSP00000457386.1
SMIM1	ENST00000561886.2	c.-75-136A>C		intron_variant		2		ENSP00000456559.1
SMIM1	ENST00000452264.1	c.-75-136A>C		intron_variant		2		ENSP00000457674.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47013 AN: 151658 Hom.: 8951 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.00252

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.223 AC: 72701 AN: 326306 Hom.: 9658 AF XY: 0.219 AC XY: 37468 AN XY: 171108

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.000422

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.310 AC: 47095 AN: 151776 Hom.: 8975 Cov.: 31 AF XY: 0.307 AC XY: 22753 AN XY: 74190

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.00252

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.280

Alfa AF: 0.245 Hom.: 6484

Bravo AF: 0.310

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1175549; hg19: chr1-3691727;