dbSNP rs3759757: ENSG00000259502:n.125G>C (chr14-67611110-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000559594.1(ENSG00000259502):n.125G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 154,256 control chromosomes in the GnomAD database, including 18,079 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 0.43 ( 17956 hom., cov: 31)

Exomes 𝑓: 0.31 ( 123 hom. )

Consequence

ENSG00000259502
ENST00000559594.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.985

Publications

8 publications found

Variant links:

Genes affected

ENSG00000259502 (HGNC:):

ENSG00000259502 links:

GPHN (HGNC:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

GPHN Gene-Disease associations (from GenCC):

sulfite oxidase deficiency due to molybdenum cofactor deficiency type C
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
hereditary hyperekplexia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

GPHN 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100419668		n.67611110G>C		intragenic_variant
GPHN	XM_047430879.1 link	c.1313-124085G>C		intron_variant	Intron 14 of 14		XP_047286835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000259502	ENST00000559594.1 link	n.125G>C		non_coding_transcript_exon_variant	Exon 1 of 3	6

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65181

AN:

151834

Hom.:

17900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.436

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.436

GnomAD4 exome

AF:

0.306

AC:

704

AN:

2304

Hom.:

123

Cov.:

AF XY:

0.305

AC XY:

340

AN XY:

1114

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AF:

0.348

AC:

AN:

European-Finnish (FIN)

AF:

0.256

AC:

367

AN:

1432

Middle Eastern (MID)

AF:

0.420

AC:

189

AN:

450

European-Non Finnish (NFE)

AF:

0.268

AC:

AN:

280

Other (OTH)

AF:

0.576

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.430

AC:

65307

AN:

151952

Hom.:

17956

Cov.:

AF XY:

0.427

AC XY:

31680

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.787

AC:

32614

AN:

41442

American (AMR)

AF:

0.389

AC:

5940

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

1034

AN:

3462

East Asian (EAS)

AF:

0.436

AC:

2251

AN:

5160

South Asian (SAS)

AF:

0.356

AC:

1708

AN:

4804

European-Finnish (FIN)

AF:

0.290

AC:

3062

AN:

10570

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17513

AN:

67944

Other (OTH)

AF:

0.441

AC:

929

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1462

2923

4385

5846

7308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.362

Hom.:

1624

Bravo

AF:

0.457

Asia WGS

AF:

0.428

AC:

1491

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.5

(source)

DANN

Benign

0.40

PhyloP100

-0.98

Splicing

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