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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003938.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBM	NM_001003938.4	MANE Select	c.*35C>A		3_prime_UTR	Exon 3 of 3	NP_001003938.1	Q6B0K9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HBM	ENST00000356815.4	TSL:1 MANE Select	c.*35C>A	3_prime_UTR	Exon 3 of 3	ENSP00000349270.3	Q6B0K9
HBM	ENST00000472539.5	TSL:5	n.574C>A	non_coding_transcript_exon	Exon 3 of 3
HBM	ENST00000496585.1	TSL:2	n.574C>A	non_coding_transcript_exon	Exon 3 of 3

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over