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. Variant has been reported in ClinVar as (no stars).

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.

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.225+86G>A	intron	N/A	NP_001136028.1	O75330-3
HMMR	NM_012484.3		c.225+86G>A	intron	N/A	NP_036616.2	O75330-1
HMMR	NM_012485.3		c.225+86G>A	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.225+86G>A	intron	N/A	ENSP00000377492.4	O75330-3
HMMR	ENST00000358715.3	TSL:1	c.225+86G>A	intron	N/A	ENSP00000351554.3	O75330-1
HMMR	ENST00000353866.7	TSL:1	c.225+86G>A	intron	N/A	ENSP00000185942.6	O75330-2

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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