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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HMMR	NM_001142556.2 link	c.1269-110G>T	intron_variant	Intron 11 of 17	ENST00000393915.9	NP_001136028.1	O75330-3
HMMR	NM_012484.3 link	c.1266-110G>T	intron_variant	Intron 11 of 17		NP_036616.2	O75330-1
HMMR	NM_012485.3 link	c.1221-110G>T	intron_variant	Intron 10 of 16		NP_036617.2	O75330-2
HMMR	NM_001142557.2 link	c.1008-110G>T	intron_variant	Intron 8 of 14		NP_001136029.1	O75330-4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HMMR	ENST00000393915.9 link	c.1269-110G>T	intron_variant	Intron 11 of 17	1	NM_001142556.2	ENSP00000377492.4	O75330-3
HMMR	ENST00000358715.3 link	c.1266-110G>T	intron_variant	Intron 11 of 17	1		ENSP00000351554.3	O75330-1
HMMR	ENST00000353866.7 link	c.1221-110G>T	intron_variant	Intron 10 of 16	1		ENSP00000185942.6	O75330-2
HMMR	ENST00000432118.6 link	c.1008-110G>T	intron_variant	Intron 8 of 14	2		ENSP00000402673.2	O75330-4

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

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

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 v4.3

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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5-163478574-G-T

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