dbSNP rs299283: HMMR:c.462+21T>C (chr5-163469850-T-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_001142556.2(HMMR):c.462+21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,482,654 control chromosomes in the GnomAD database, including 81,992 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 0.39 ( 12812 hom., cov: 33)

Exomes 𝑓: 0.31 ( 69180 hom. )

Consequence

HMMR
NM_001142556.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.274

Publications

9 publications found

Variant links:

Genes affected

HMMR (HGNC:5012): (hyaluronan mediated motility receptor) The protein encoded by this gene is involved in cell motility. It is expressed in breast tissue and together with other proteins, it forms a complex with BRCA1 and BRCA2, thus is potentially associated with higher risk of breast cancer. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Dec 2008]

HMMR links:

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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 (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HMMR	NM_001142556.2 link	c.462+21T>C	intron_variant	Intron 5 of 17	ENST00000393915.9	NP_001136028.1	O75330-3
HMMR	NM_012484.3 link	c.459+21T>C	intron_variant	Intron 5 of 17		NP_036616.2	O75330-1
HMMR	NM_012485.3 link	c.414+21T>C	intron_variant	Intron 4 of 16		NP_036617.2	O75330-2
HMMR	NM_001142557.2 link	c.201+21T>C	intron_variant	Intron 2 of 14		NP_001136029.1	O75330-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000393915.9 link	c.462+21T>C		intron_variant	Intron 5 of 17	1	NM_001142556.2	ENSP00000377492.4		O75330-3
HMMR	ENST00000520345.5 link	c.117+21T>C		intron_variant	Intron 4 of 5	2		ENSP00000428481.1		E5RI30

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59505

AN:

152010

Hom.:

12785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.341

GnomAD2 exomes

AF:

0.353

AC:

82195

AN:

232668

AF XY:

0.344

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.383

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.556

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.314

AC:

417622

AN:

1330528

Hom.:

69180

Cov.:

AF XY:

0.312

AC XY:

208421

AN XY:

667786

show subpopulations

African (AFR)

AF:

0.574

AC:

16963

AN:

29572

American (AMR)

AF:

0.371

AC:

14068

AN:

37914

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

6290

AN:

24542

East Asian (EAS)

AF:

0.568

AC:

22006

AN:

38746

South Asian (SAS)

AF:

0.299

AC:

24349

AN:

81382

European-Finnish (FIN)

AF:

0.358

AC:

19000

AN:

53080

Middle Eastern (MID)

AF:

0.316

AC:

1713

AN:

5426

European-Non Finnish (NFE)

AF:

0.294

AC:

295081

AN:

1004142

Other (OTH)

AF:

0.326

AC:

18152

AN:

55724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

13357

26714

40072

53429

66786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9632

19264

28896

38528

48160

<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:

0.392

AC:

59580

AN:

152126

Hom.:

12812

Cov.:

AF XY:

0.394

AC XY:

29269

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.574

AC:

23810

AN:

41486

American (AMR)

AF:

0.347

AC:

5294

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

904

AN:

3468

East Asian (EAS)

AF:

0.545

AC:

2825

AN:

5182

South Asian (SAS)

AF:

0.302

AC:

1459

AN:

4826

European-Finnish (FIN)

AF:

0.363

AC:

3839

AN:

10578

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.299

AC:

20324

AN:

67994

Other (OTH)

AF:

0.350

AC:

739

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1773

3545

5318

7090

8863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.318

Hom.:

5857

Bravo

AF:

0.400

Asia WGS

AF:

0.433

AC:

1503

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.7

(source)

DANN

Benign

0.60

PhyloP100

-0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

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