rs299284

Positions:

• chr5-163469644-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000520345(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_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HMMR	NM_001142556.2	c.277C>T	p.Arg93Cys	missense_variant	5/18	ENST00000393915.9	NP_001136028.1
HMMR	NM_012484.3	c.274C>T	p.Arg92Cys	missense_variant	5/18		NP_036616.2
HMMR	NM_012485.3	c.229C>T	p.Arg77Cys	missense_variant	4/17		NP_036617.2
HMMR	NM_001142557.2	c.16C>T	p.Arg6Cys	missense_variant	2/15		NP_001136029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000520345	c.-69C>T		5_prime_UTR_premature_start_codon_gain_variant	4/6	2		ENSP00000428481.1
HMMR	ENST00000393915.9	c.277C>T	p.Arg93Cys	missense_variant	5/18	1	NM_001142556.2	ENSP00000377492.4
HMMR	ENST00000520345	c.-69C>T		5_prime_UTR_variant	4/6	2		ENSP00000428481.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15590 AN: 152000 Hom.: 855 Cov.: 32

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

GnomAD3 exomes AF: 0.0992 AC: 24368 AN: 245592 Hom.: 1404 AF XY: 0.102 AC XY: 13576 AN XY: 132980

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 SAS exome AF: 0.101

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.: 30 AF XY: 0.106 AC XY: 76730 AN XY: 723380

Gnomad4 AFR exome AF: 0.0927

Gnomad4 AMR exome AF: 0.0608

Gnomad4 ASJ exome AF: 0.0980

Gnomad4 EAS exome AF: 0.0156

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.102 AC: 15588 AN: 152118 Hom.: 852 Cov.: 32 AF XY: 0.103 AC XY: 7647 AN XY: 74346

Gnomad4 AFR AF: 0.0911

Gnomad4 AMR AF: 0.0824

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0128

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0981

Alfa AF: 0.112 Hom.: 2499

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	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.44	.;.;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T;D;D;D
MetaRNN	Benign	0.0026	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.7	.;.;.;M
PrimateAI	Uncertain	0.55	T
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	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.54
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs299284; hg19: chr5-162896650; COSMIC: COSV62374209; COSMIC: COSV62374209;