Genetic Variant SMIM1:c.-75-136A>C (chr1-3775163-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

22 publications found

Variant links:

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]

SMIM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMIM1	NM_001288583.2 link	c.-75-136A>C		intron_variant	Intron 2 of 3	ENST00000642557.4	NP_001275512.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SMIM1	ENST00000642557.4 link	c.-75-136A>C	intron_variant	Intron 2 of 3		NM_001288583.2	ENSP00000496314.2
SMIM1	ENST00000444870.7 link	c.-75-136A>C	intron_variant	Intron 2 of 3	1		ENSP00000457386.1
SMIM1	ENST00000561886.2 link	c.-75-136A>C	intron_variant	Intron 2 of 2	2		ENSP00000456559.1
SMIM1	ENST00000452264.1 link	c.-75-136A>C	intron_variant	Intron 1 of 1	2		ENSP00000457674.1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47013

AN:

151658

Hom.:

8951

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.525

AC:

5067

AN:

9648

American (AMR)

AF:

0.156

AC:

2299

AN:

14710

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

2589

AN:

10086

East Asian (EAS)

AF:

0.000422

AC:

AN:

23720

South Asian (SAS)

AF:

0.169

AC:

5723

AN:

33768

European-Finnish (FIN)

AF:

0.284

AC:

6150

AN:

21646

Middle Eastern (MID)

AF:

0.237

AC:

374

AN:

1580

European-Non Finnish (NFE)

AF:

0.238

AC:

45763

AN:

192052

Other (OTH)

AF:

0.247

AC:

4726

AN:

19096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

2492

4984

7475

9967

12459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.310

AC:

47095

AN:

151776

Hom.:

8975

Cov.:

AF XY:

0.307

AC XY:

22753

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.525

AC:

21706

AN:

41352

American (AMR)

AF:

0.190

AC:

2906

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

970

AN:

3470

East Asian (EAS)

AF:

0.00252

AC:

AN:

5154

South Asian (SAS)

AF:

0.171

AC:

820

AN:

4804

European-Finnish (FIN)

AF:

0.302

AC:

3182

AN:

10552

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16679

AN:

67876

Other (OTH)

AF:

0.280

AC:

589

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1492

2984

4475

5967

7459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.258

Hom.:

18090

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

(source)

DANN

Benign

0.47

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over