Genetic Variant ENST00000520345.5:c.-69C>T (chr5-163469644-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000520345.5(HMMR):c.-69C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.105 in 1,605,700 control chromosomes in the GnomAD database, including 9,376 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 0.10 ( 852 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8524 hom. )

Consequence

HMMR
ENST00000520345.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.93

Publications

30 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMMR	NM_001142556.2 link	c.277C>T	p.Arg93Cys	missense_variant	Exon 5 of 18	ENST00000393915.9	NP_001136028.1	O75330-3
HMMR	NM_012484.3 link	c.274C>T	p.Arg92Cys	missense_variant	Exon 5 of 18		NP_036616.2	O75330-1
HMMR	NM_012485.3 link	c.229C>T	p.Arg77Cys	missense_variant	Exon 4 of 17		NP_036617.2	O75330-2
HMMR	NM_001142557.2 link	c.16C>T	p.Arg6Cys	missense_variant	Exon 2 of 15		NP_001136029.1	O75330-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HMMR	ENST00000520345.5 link	c.-69C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 4 of 6	2		ENSP00000428481.1	E5RI30
HMMR	ENST00000393915.9 link	c.277C>T	p.Arg93Cys	missense_variant	Exon 5 of 18	1	NM_001142556.2	ENSP00000377492.4	O75330-3
HMMR	ENST00000520345.5 link	c.-69C>T		5_prime_UTR_variant	Exon 4 of 6	2		ENSP00000428481.1	E5RI30

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15590

AN:

152000

Hom.:

855

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0914

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.0826

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0127

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.0967

GnomAD2 exomes

AF:

0.0992

AC:

24368

AN:

245592

AF XY:

0.102

show subpopulations

Gnomad AFR exome

AF:

0.0904

Gnomad AMR exome

AF:

0.0590

Gnomad ASJ exome

AF:

0.0981

Gnomad EAS exome

AF:

0.00810

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.106

AC:

153415

AN:

1453582

Hom.:

8524

Cov.:

AF XY:

0.106

AC XY:

76730

AN XY:

723380

show subpopulations

African (AFR)

AF:

0.0927

AC:

3052

AN:

32938

American (AMR)

AF:

0.0608

AC:

2581

AN:

42424

Ashkenazi Jewish (ASJ)

AF:

0.0980

AC:

2538

AN:

25890

East Asian (EAS)

AF:

0.0156

AC:

619

AN:

39642

South Asian (SAS)

AF:

0.102

AC:

8664

AN:

85150

European-Finnish (FIN)

AF:

0.126

AC:

6751

AN:

53396

Middle Eastern (MID)

AF:

0.127

AC:

729

AN:

5734

European-Non Finnish (NFE)

AF:

0.110

AC:

122288

AN:

1108322

Other (OTH)

AF:

0.103

AC:

6193

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

5900

11800

17700

23600

29500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4256

8512

12768

17024

21280

<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:

0.102

AC:

15588

AN:

152118

Hom.:

852

Cov.:

AF XY:

0.103

AC XY:

7647

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0911

AC:

3782

AN:

41500

American (AMR)

AF:

0.0824

AC:

1259

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

372

AN:

3472

East Asian (EAS)

AF:

0.0128

AC:

AN:

5174

South Asian (SAS)

AF:

0.100

AC:

482

AN:

4816

European-Finnish (FIN)

AF:

0.113

AC:

1199

AN:

10570

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

8040

AN:

67994

Other (OTH)

AF:

0.0981

AC:

207

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

722

1445

2167

2890

3612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<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:

0.110

Hom.:

4608

Bravo

AF:

0.0978

TwinsUK

AF:

0.105

AC:

390

ALSPAC

AF:

0.109

AC:

421

ESP6500AA

AF:

0.0887

AC:

391

ESP6500EA

AF:

0.118

AC:

1012

ExAC

AF:

0.104

AC:

12593

Asia WGS

AF:

0.0650

AC:

227

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

.;.;.;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

T;D;D;D

MetaRNN

Benign

0.0026

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.7

.;.;.;M

PhyloP100

5.9

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-5.4

D;D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.75

MPC

0.42

ClinPred

0.016

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.54

gMVP

0.39

Mutation Taster

=79/21

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.41

Position offset: 15

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