dbSNP rs2858935: HBM:n.206-412G>C (chr16-165856-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000496585.1(HBM):n.206-412G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 633,098 control chromosomes in the GnomAD database, including 29,798 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 ( 7281 hom., cov: 33)

Exomes 𝑓: 0.30 ( 22517 hom. )

Consequence

HBM
ENST00000496585.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.722

Publications

8 publications found

Variant links:

COSMIC-nc: COSV61575266

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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000496585.1. 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.-142G>C		upstream_gene	N/A	NP_001003938.1	Q6B0K9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HBM	ENST00000472539.5	TSL:5	n.206-412G>C	intron	N/A
HBM	ENST00000496585.1	TSL:2	n.206-412G>C	intron	N/A
HBM	ENST00000356815.4	TSL:1 MANE Select	c.-142G>C	upstream_gene	N/A	ENSP00000349270.3	Q6B0K9

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46768

AN:

152092

Hom.:

7265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.302

AC:

145042

AN:

480892

Hom.:

22517

AF XY:

0.305

AC XY:

76922

AN XY:

252006

show subpopulations

African (AFR)

AF:

0.357

AC:

4477

AN:

12556

American (AMR)

AF:

0.299

AC:

6431

AN:

21514

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

4540

AN:

14372

East Asian (EAS)

AF:

0.362

AC:

10967

AN:

30288

South Asian (SAS)

AF:

0.372

AC:

17660

AN:

47444

European-Finnish (FIN)

AF:

0.243

AC:

7213

AN:

29680

Middle Eastern (MID)

AF:

0.321

AC:

670

AN:

2084

European-Non Finnish (NFE)

AF:

0.287

AC:

84905

AN:

295820

Other (OTH)

AF:

0.301

AC:

8179

AN:

27134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

5369

10738

16107

21476

26845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.308

AC:

46825

AN:

152206

Hom.:

7281

Cov.:

AF XY:

0.306

AC XY:

22765

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.355

AC:

14741

AN:

41528

American (AMR)

AF:

0.299

AC:

4582

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1071

AN:

3470

East Asian (EAS)

AF:

0.311

AC:

1603

AN:

5160

South Asian (SAS)

AF:

0.371

AC:

1789

AN:

4826

European-Finnish (FIN)

AF:

0.243

AC:

2575

AN:

10616

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19427

AN:

67988

Other (OTH)

AF:

0.314

AC:

664

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1768

3536

5305

7073

8841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.176

Hom.:

353

Bravo

AF:

0.312

Asia WGS

AF:

0.399

AC:

1387

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.8

(source)

DANN

Benign

0.22

PhyloP100

-0.72

PromoterAI

0.0049

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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