Variant 6-49606843-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000324.3(RHAG):c.1212+5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000708 in 1,581,584 control chromosomes in the GnomAD database, including 3 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00067 ( 3 hom. )

Consequence

RHAG
NM_000324.3 splice_region, intron

Scores

Splicing: ADA: 0.001651

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.500

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005898595).

BP6

Variant 6-49606843-A-G is Benign according to our data. Variant chr6-49606843-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2727778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00104 (158/152194) while in subpopulation NFE AF= 0.00106 (72/68042). AF 95% confidence interval is 0.000861. There are 0 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR,BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHAG	NM_000324.3 link	c.1212+5T>C		splice_region_variant, intron_variant	Intron 9 of 9	ENST00000371175.10	NP_000315.2	Q02094-1Q96E98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RHAG	ENST00000371175.10 link	c.1212+5T>C		splice_region_variant, intron_variant	Intron 9 of 9	1	NM_000324.3	ENSP00000360217.4	Q02094-1
RHAG	ENST00000646272.1 link	c.1217T>C	p.Leu406Pro	missense_variant	Exon 9 of 10			ENSP00000494337.1	A0A2R8YEH1
RHAG	ENST00000646963.1 link	c.1138+307T>C		intron_variant	Intron 8 of 8			ENSP00000495337.1	Q9UHG9
RHAG	ENST00000646939.1 link	c.*34+5T>C		splice_region_variant, intron_variant	Intron 8 of 8			ENSP00000494709.1	Q02094-2

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

158

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00781

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00104

AC:

261

AN:

250582

Hom.:

AF XY:

0.000989

AC XY:

134

AN XY:

135422

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00717

Gnomad NFE exome

AF:

0.000901

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000672

AC:

961

AN:

1429390

Hom.:

Cov.:

AF XY:

0.000679

AC XY:

484

AN XY:

713264

show subpopulations

Gnomad4 AFR exome

AF:

0.0000609

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00748

Gnomad4 NFE exome

AF:

0.000492

Gnomad4 OTH exome

AF:

0.000422

GnomAD4 genome

AF:

0.00104

AC:

158

AN:

152194

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

100

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00781

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000881

Hom.:

Bravo

AF:

0.000389

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000857

AC:

104

EpiCase

AF:

0.000764

EpiControl

AF:

0.000534

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RHAG: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.80

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.21

MetaRNN

Benign

0.0059

GERP RS

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0017

dbscSNV1_RF

Benign

0.070

SpliceAI score (max)

0.090

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