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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142556.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMMR	NM_001142556.2	MANE Select	c.462+21T>C	intron	N/A	NP_001136028.1	O75330-3
HMMR	NM_012484.3		c.459+21T>C	intron	N/A	NP_036616.2	O75330-1
HMMR	NM_012485.3		c.414+21T>C	intron	N/A	NP_036617.2	O75330-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMMR	ENST00000393915.9	TSL:1 MANE Select	c.462+21T>C	intron	N/A	ENSP00000377492.4	O75330-3
HMMR	ENST00000358715.3	TSL:1	c.459+21T>C	intron	N/A	ENSP00000351554.3	O75330-1
HMMR	ENST00000353866.7	TSL:1	c.414+21T>C	intron	N/A	ENSP00000185942.6	O75330-2

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over