dbSNP rs3756648: HMMR:c.225+86G>A (chr5-163464888-G-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_001142556.2(HMMR):c.225+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 809,290 control chromosomes in the GnomAD database, including 78,685 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 0.41 ( 13424 hom., cov: 33)

Exomes 𝑓: 0.44 ( 65261 hom. )

Consequence

HMMR
NM_001142556.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.656

Publications

8 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:

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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HMMR	NM_001142556.2 link	c.225+86G>A	intron_variant	Intron 3 of 17	ENST00000393915.9	NP_001136028.1	O75330-3
HMMR	NM_012484.3 link	c.225+86G>A	intron_variant	Intron 3 of 17		NP_036616.2	O75330-1
HMMR	NM_012485.3 link	c.225+86G>A	intron_variant	Intron 3 of 16		NP_036617.2	O75330-2
HMMR	NM_001142557.2 link	c.12+4150G>A	intron_variant	Intron 1 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.225+86G>A		intron_variant	Intron 3 of 17	1	NM_001142556.2	ENSP00000377492.4		O75330-3
HMMR	ENST00000520345.5 link	c.-73+86G>A		intron_variant	Intron 3 of 5	2		ENSP00000428481.1		E5RI30

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62557

AN:

151950

Hom.:

13421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.434

GnomAD4 exome

AF:

0.435

AC:

286199

AN:

657222

Hom.:

65261

Cov.:

AF XY:

0.429

AC XY:

150986

AN XY:

351812

show subpopulations

African (AFR)

AF:

0.317

AC:

5170

AN:

16324

American (AMR)

AF:

0.439

AC:

13941

AN:

31726

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

7563

AN:

18482

East Asian (EAS)

AF:

0.164

AC:

5788

AN:

35188

South Asian (SAS)

AF:

0.267

AC:

16921

AN:

63470

European-Finnish (FIN)

AF:

0.445

AC:

21460

AN:

48244

Middle Eastern (MID)

AF:

0.412

AC:

1317

AN:

3194

European-Non Finnish (NFE)

AF:

0.490

AC:

199544

AN:

407316

Other (OTH)

AF:

0.436

AC:

14495

AN:

33278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

7533

15066

22598

30131

37664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2354

4708

7062

9416

11770

<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:

0.411

AC:

62571

AN:

152068

Hom.:

13424

Cov.:

AF XY:

0.406

AC XY:

30187

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.313

AC:

12972

AN:

41446

American (AMR)

AF:

0.447

AC:

6836

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1370

AN:

3466

East Asian (EAS)

AF:

0.182

AC:

943

AN:

5192

South Asian (SAS)

AF:

0.282

AC:

1358

AN:

4824

European-Finnish (FIN)

AF:

0.429

AC:

4535

AN:

10574

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.487

AC:

33098

AN:

67964

Other (OTH)

AF:

0.429

AC:

907

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1872

3743

5615

7486

9358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.448

Hom.:

3086

Bravo

AF:

0.411

Asia WGS

AF:

0.267

AC:

930

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.4

(source)

DANN

Benign

0.47

PhyloP100

0.66

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