Genetic Variant TRPV6:c.248+3205A>G (chr7-142882184-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018646.6(TRPV6):c.248+3205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,368 control chromosomes in the GnomAD database, including 6,364 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 0.20 ( 6362 hom., cov: 32)

Exomes 𝑓: 0.093 ( 2 hom. )

Consequence

TRPV6
NM_018646.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.532

Publications

3 publications found

Variant links:

Genes affected

TRPV6 (HGNC:14006): (transient receptor potential cation channel subfamily V member 6) This gene encodes a member of a family of multipass membrane proteins that functions as calcium channels. The encoded protein contains N-terminal ankyrin repeats, which are required for channel assembly and regulation. Translation initiation for this protein occurs at a non-AUG start codon that is decoded as methionine. This gene is situated next to a closely related gene for transient receptor potential cation channel subfamily V member 5 (TRPV5). This locus has experienced positive selection in non-African populations, resulting in several non-synonymous codon differences among individuals of different genetic backgrounds. [provided by RefSeq, Feb 2015]

TRPV6 Gene-Disease associations (from GenCC):

hyperparathyroidism, transient neonatal
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P
intestinal hypomagnesemia 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
pancreatitis
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
neonatal severe primary hyperparathyroidism
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TRPV6 links:

ENSG00000224970 (HGNC:):

ENSG00000224970 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV6	NM_018646.6 link	c.248+3205A>G		intron_variant	Intron 1 of 14	ENST00000359396.9	NP_061116.5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
TRPV6	ENST00000359396.9 link	c.248+3205A>G	intron_variant	Intron 1 of 14	1	NM_018646.6	ENSP00000352358.5
TRPV6	ENST00000436401.1 link	c.-68+3463A>G	intron_variant	Intron 1 of 5	4		ENSP00000411100.1
TRPV6	ENST00000615386.4 link	n.3206A>G	non_coding_transcript_exon_variant	Exon 1 of 12	2
ENSG00000224970	ENST00000438839.2 link	n.99+6250T>C	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30428

AN:

152004

Hom.:

6342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.533

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0649

Gnomad EAS

AF:

0.0214

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0729

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0768

Gnomad OTH

AF:

0.179

GnomAD4 exome

AF:

0.0935

AC:

AN:

246

Hom.:

Cov.:

AF XY:

0.0811

AC XY:

AN XY:

148

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0294

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

AN:

140

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.200

AC:

30491

AN:

152122

Hom.:

6362

Cov.:

AF XY:

0.192

AC XY:

14319

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.533

AC:

22106

AN:

41440

American (AMR)

AF:

0.102

AC:

1559

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0649

AC:

225

AN:

3468

East Asian (EAS)

AF:

0.0214

AC:

111

AN:

5180

South Asian (SAS)

AF:

0.0122

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0729

AC:

773

AN:

10604

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0768

AC:

5219

AN:

67994

Other (OTH)

AF:

0.177

AC:

374

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

921

1842

2764

3685

4606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.152

Hom.:

780

Bravo

AF:

0.219

Asia WGS

AF:

0.0570

AC:

200

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.9

(source)

DANN

Benign

0.40

PhyloP100

-0.53

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over