Genetic Variant NM_014211.3:c.*1161A>C (chr5-170813419-A-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_014211.3(GABRP):c.*1161A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,280 control chromosomes in the GnomAD database, including 50,908 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 0.82 ( 50881 hom., cov: 33)

Exomes 𝑓: 0.83 ( 27 hom. )

Consequence

GABRP
NM_014211.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

6 publications found

Variant links:

Genes affected

GABRP (HGNC:4089): (gamma-aminobutyric acid type A receptor subunit pi) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. The subunit encoded by this gene is expressed in several non-neuronal tissues including the uterus and ovaries. This subunit can assemble with known GABA A receptor subunits, and the presence of this subunit alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

GABRP 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GABRP	NM_014211.3 link	c.*1161A>C	3_prime_UTR_variant	Exon 10 of 10	ENST00000265294.9	NP_055026.1
GABRP	NM_001291985.2 link	c.*1426A>C	3_prime_UTR_variant	Exon 9 of 9		NP_001278914.1	O00591B4DTP4E7EWG0
GABRP	XM_024446012.2 link	c.*1161A>C	3_prime_UTR_variant	Exon 10 of 10		XP_024301780.1
GABRP	XM_005265872.2 link	c.*1161A>C	3_prime_UTR_variant	Exon 8 of 8		XP_005265929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRP	ENST00000265294.9 link	c.*1161A>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_014211.3	ENSP00000265294.4		O00591
GABRP	ENST00000518525.5 link	c.*1161A>C		3_prime_UTR_variant	Exon 11 of 11	5		ENSP00000430100.1		O00591

Frequencies

GnomAD3 genomes

AF:

0.816

AC:

124046

AN:

152084

Hom.:

50834

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.739

Gnomad AMR

AF:

0.842

Gnomad ASJ

AF:

0.866

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.945

Gnomad FIN

AF:

0.796

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.818

Gnomad OTH

AF:

0.820

GnomAD4 exome

AF:

0.833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.879

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.827

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.580

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.816

AC:

124146

AN:

152202

Hom.:

50881

Cov.:

AF XY:

0.820

AC XY:

60982

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.765

AC:

31785

AN:

41528

American (AMR)

AF:

0.842

AC:

12880

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.866

AC:

3006

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5171

AN:

5180

South Asian (SAS)

AF:

0.946

AC:

4566

AN:

4828

European-Finnish (FIN)

AF:

0.796

AC:

8431

AN:

10590

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.818

AC:

55657

AN:

68002

Other (OTH)

AF:

0.821

AC:

1735

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1168

2336

3503

4671

5839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.816

Hom.:

77791

Bravo

AF:

0.816

Asia WGS

AF:

0.955

AC:

3321

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.16

(source)

DANN

Benign

0.66

PhyloP100

-1.6

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