Variant 6-49606928-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000324.3(RHAG):c.1139-7G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,601,902 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 7 hom. )

Consequence

RHAG
NM_000324.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003437

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.870

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-49606928-C-T is Benign according to our data. Variant chr6-49606928-C-T is described in ClinVar as [Benign]. Clinvar id is 1670237.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-49606928-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00158 (241/152162) while in subpopulation NFE AF= 0.0024 (163/68002). AF 95% confidence interval is 0.0021. There are 2 homozygotes in gnomad4. There are 98 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR,BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHAG	NM_000324.3 linkuse as main transcript	c.1139-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000371175.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RHAG	ENST00000371175.10 linkuse as main transcript	c.1139-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_000324.3	P2	Q02094-1
RHAG	ENST00000646272.1 linkuse as main transcript	c.1139-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			A2
RHAG	ENST00000646939.1 linkuse as main transcript	c.1017-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				Q02094-2
RHAG	ENST00000646963.1 linkuse as main transcript	c.1138+222G>A	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

241

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00185

AC:

465

AN:

250744

Hom.:

AF XY:

0.00187

AC XY:

253

AN XY:

135506

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00272

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.00281

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00240

AC:

3477

AN:

1449740

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

1682

AN XY:

722030

show subpopulations

Gnomad4 AFR exome

AF:

0.000784

Gnomad4 AMR exome

AF:

0.000694

Gnomad4 ASJ exome

AF:

0.000460

Gnomad4 EAS exome

AF:

0.00101

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00259

Gnomad4 NFE exome

AF:

0.00280

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.00158

AC:

241

AN:

152162

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000771

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.00240

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00194

Hom.:

Bravo

AF:

0.00146

EpiCase

AF:

0.00338

EpiControl

AF:

0.00427

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.28

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000034

dbscSNV1_RF

Benign

0.0020

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

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