Genetic Variant HMMR:c.1269-110G>T (chr5-163478574-G-T) – 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.1269-110G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 699,182 control chromosomes in the GnomAD database, including 18,825 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 0.18 ( 2998 hom., cov: 32)

Exomes 𝑓: 0.23 ( 15827 hom. )

Consequence

HMMR
NM_001142556.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.219

Publications

5 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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 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.1269-110G>T	intron	N/A	NP_001136028.1	O75330-3
HMMR	NM_012484.3		c.1266-110G>T	intron	N/A	NP_036616.2	O75330-1
HMMR	NM_012485.3		c.1221-110G>T	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.1269-110G>T	intron	N/A	ENSP00000377492.4	O75330-3
HMMR	ENST00000358715.3	TSL:1	c.1266-110G>T	intron	N/A	ENSP00000351554.3	O75330-1
HMMR	ENST00000353866.7	TSL:1	c.1221-110G>T	intron	N/A	ENSP00000185942.6	O75330-2

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28133

AN:

152002

Hom.:

3002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0929

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.229

AC:

125118

AN:

547062

Hom.:

15827

AF XY:

0.238

AC XY:

70209

AN XY:

295364

show subpopulations

African (AFR)

AF:

0.0956

AC:

1428

AN:

14936

American (AMR)

AF:

0.183

AC:

5898

AN:

32264

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

5284

AN:

16062

East Asian (EAS)

AF:

0.266

AC:

9159

AN:

34406

South Asian (SAS)

AF:

0.395

AC:

22154

AN:

56022

European-Finnish (FIN)

AF:

0.196

AC:

8795

AN:

44970

Middle Eastern (MID)

AF:

0.252

AC:

682

AN:

2710

European-Non Finnish (NFE)

AF:

0.206

AC:

65258

AN:

316508

Other (OTH)

AF:

0.221

AC:

6460

AN:

29184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

4273

8546

12820

17093

21366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.185

AC:

28133

AN:

152120

Hom.:

2998

Cov.:

AF XY:

0.188

AC XY:

13994

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0929

AC:

3857

AN:

41510

American (AMR)

AF:

0.194

AC:

2963

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

1180

AN:

3468

East Asian (EAS)

AF:

0.273

AC:

1416

AN:

5182

South Asian (SAS)

AF:

0.381

AC:

1832

AN:

4814

European-Finnish (FIN)

AF:

0.207

AC:

2186

AN:

10552

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

14012

AN:

67992

Other (OTH)

AF:

0.209

AC:

442

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1132

2263

3395

4526

5658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.190

Hom.:

753

Bravo

AF:

0.178

Asia WGS

AF:

0.282

AC:

983

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

(source)

DANN

Benign

0.54

PhyloP100

-0.22

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