dbSNP rs75368786: HBM:c.*35C>A (chr16-166743-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001003938.4(HBM):c.*35C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,610,788 control chromosomes in the GnomAD database, including 179 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 0.0038 ( 26 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 153 hom. )

Consequence

HBM
NM_001003938.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.930

Publications

3 publications found

Variant links:

Genes affected

HBM (HGNC:4826): (hemoglobin subunit mu) The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5'- zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta - 3'. This gene has an ORF encoding a 141 aa polypeptide which is similar to the delta globins found in reptiles and birds. This locus was originally described as a pseudogene; however, it is currently thought to be a protein-coding gene. [provided by RefSeq, Jul 2008]

HBM 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=-0.61).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBM	NM_001003938.4 link	c.*35C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000356815.4	NP_001003938.1	Q6B0K9A0A1K0FU50

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HBM	ENST00000356815.4 link	c.*35C>A	3_prime_UTR_variant	Exon 3 of 3	1	NM_001003938.4	ENSP00000349270.3	Q6B0K9
HBM	ENST00000472539.5 link	n.574C>A	non_coding_transcript_exon_variant	Exon 3 of 3	5
HBM	ENST00000496585.1 link	n.574C>A	non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00384

AC:

584

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0785

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.00255

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00919

AC:

2238

AN:

243478

AF XY:

0.00803

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.0164

Gnomad ASJ exome

AF:

0.00354

Gnomad EAS exome

AF:

0.0792

Gnomad FIN exome

AF:

0.00301

Gnomad NFE exome

AF:

0.000457

Gnomad OTH exome

AF:

0.00534

GnomAD4 exome

AF:

0.00306

AC:

4469

AN:

1458492

Hom.:

153

Cov.:

AF XY:

0.00296

AC XY:

2150

AN XY:

725322

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33382

American (AMR)

AF:

0.0144

AC:

639

AN:

44320

Ashkenazi Jewish (ASJ)

AF:

0.00322

AC:

AN:

26068

East Asian (EAS)

AF:

0.0713

AC:

2815

AN:

39508

South Asian (SAS)

AF:

0.00333

AC:

285

AN:

85630

European-Finnish (FIN)

AF:

0.00314

AC:

167

AN:

53200

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000197

AC:

219

AN:

1110382

Other (OTH)

AF:

0.00422

AC:

254

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

239

478

716

955

1194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.00383

AC:

584

AN:

152296

Hom.:

Cov.:

AF XY:

0.00410

AC XY:

305

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41564

American (AMR)

AF:

0.00542

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.0786

AC:

407

AN:

5176

South Asian (SAS)

AF:

0.00435

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00255

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68026

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00139

Hom.:

Bravo

AF:

0.00484

Asia WGS

AF:

0.0290

AC:

102

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.0

(source)

DANN

Benign

0.72

PhyloP100

0.93

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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