Variant 6-49607246-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_000324.3(RHAG):c.1068-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,596,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

RHAG
NM_000324.3 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.940

Variant links:

Genes affected

RHAG (HGNC:10006): (Rh associated glycoprotein) The protein encoded by this gene is erythrocyte-specific and is thought to be part of a membrane channel that transports ammonium and carbon dioxide across the blood cell membrane. The encoded protein appears to interact with Rh blood group antigens and Rh30 polypeptides. Defects in this gene are a cause of regulator type Rh-null hemolytic anemia (RHN), or Rh-deficiency syndrome.[provided by RefSeq, Mar 2009]

RHAG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

This place is a probable branch point but rather VUS (scored 5 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000663 (101/152342) while in subpopulation AFR AF= 0.00236 (98/41590). AF 95% confidence interval is 0.00198. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHAG	NM_000324.3 linkuse as main transcript	c.1068-26T>C		intron_variant		ENST00000371175.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RHAG	ENST00000371175.10 linkuse as main transcript	c.1068-26T>C	intron_variant	1	NM_000324.3	P2	Q02094-1
RHAG	ENST00000646272.1 linkuse as main transcript	c.1068-26T>C	intron_variant			A2
RHAG	ENST00000646939.1 linkuse as main transcript	c.946-26T>C	intron_variant				Q02094-2
RHAG	ENST00000646963.1 linkuse as main transcript	c.1068-26T>C	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

101

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000219

AC:

AN:

242410

Hom.:

AF XY:

0.000153

AC XY:

AN XY:

130688

show subpopulations

Gnomad AFR exome

AF:

0.00329

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000672

AC:

AN:

1443694

Hom.:

Cov.:

AF XY:

0.0000543

AC XY:

AN XY:

718658

show subpopulations

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000638

Gnomad4 OTH exome

AF:

0.0000669

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152342

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000759

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Oct 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.2

DANN

Benign

0.76

BranchPoint Hunter

5.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over