Genetic Variant RHAG:c.946-100T>C (chr6-49611245-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000324.3(RHAG):c.946-100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 900,370 control chromosomes in the GnomAD database, including 969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.050 ( 279 hom., cov: 32)

Exomes 𝑓: 0.033 ( 690 hom. )

Consequence

RHAG
NM_000324.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.715

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=-0.94).

BP6

Variant 6-49611245-A-G is Benign according to our data. Variant chr6-49611245-A-G is described in ClinVar as [Benign]. Clinvar id is 1234058.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-49611245-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHAG	NM_000324.3 link	c.946-100T>C		intron_variant	Intron 6 of 9	ENST00000371175.10	NP_000315.2	Q02094-1Q96E98

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RHAG	ENST00000371175.10 link	c.946-100T>C	intron_variant	Intron 6 of 9	1	NM_000324.3	ENSP00000360217.4	Q02094-1
RHAG	ENST00000646272.1 link	c.946-100T>C	intron_variant	Intron 6 of 9			ENSP00000494337.1	A0A2R8YEH1
RHAG	ENST00000646963.1 link	c.946-100T>C	intron_variant	Intron 6 of 8			ENSP00000495337.1	Q9UHG9
RHAG	ENST00000646939.1 link	c.945+1152T>C	intron_variant	Intron 6 of 8			ENSP00000494709.1	Q02094-2

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7584

AN:

152206

Hom.:

278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.0501

Gnomad EAS

AF:

0.0575

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0239

Gnomad OTH

AF:

0.0497

GnomAD4 exome

AF:

0.0328

AC:

24505

AN:

748046

Hom.:

690

AF XY:

0.0350

AC XY:

13796

AN XY:

394502

show subpopulations

Gnomad4 AFR exome

AF:

0.0967

Gnomad4 AMR exome

AF:

0.0448

Gnomad4 ASJ exome

AF:

0.0450

Gnomad4 EAS exome

AF:

0.0492

Gnomad4 SAS exome

AF:

0.0953

Gnomad4 FIN exome

AF:

0.0131

Gnomad4 NFE exome

AF:

0.0224

Gnomad4 OTH exome

AF:

0.0342

GnomAD4 genome

AF:

0.0499

AC:

7598

AN:

152324

Hom.:

279

Cov.:

AF XY:

0.0501

AC XY:

3733

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.0361

Gnomad4 ASJ

AF:

0.0501

Gnomad4 EAS

AF:

0.0579

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.0238

Gnomad4 OTH

AF:

0.0525

Alfa

AF:

0.0386

Hom.:

Bravo

AF:

0.0533

Asia WGS

AF:

0.0770

AC:

267

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.40

DANN

Benign

0.69

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

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