6-49606641-G-T

Position:

• chr6-49606641-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000324.3(RHAG):​c.1212+207C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 483,398 control chromosomes in the GnomAD database, including 60,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (16889 hom., cov: 31)
  • Exomes 𝑓: 0.50 (43770 hom.)
• Consequence: RHAG NM_000324.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.321

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-49606641-G-T is Benign according to our data. Variant chr6-49606641-G-T is described in ClinVar as [Benign]. Clinvar id is 1221020.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHAG	NM_000324.3	c.1212+207C>A		intron_variant		ENST00000371175.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHAG	ENST00000371175.10	c.1212+207C>A		intron_variant		1	NM_000324.3	P2
RHAG	ENST00000646272.1	c.*29+88C>A		intron_variant				A2
RHAG	ENST00000646939.1	c.*34+207C>A		intron_variant
RHAG	ENST00000646963.1	c.1138+509C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66053 AN: 151794 Hom.: 16888 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.501 AC: 166132 AN: 331486 Hom.: 43770 AF XY: 0.500 AC XY: 86248 AN XY: 172452

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.513

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.492

GnomAD4 genome AF: 0.435 AC: 66077 AN: 151912 Hom.: 16889 Cov.: 31 AF XY: 0.433 AC XY: 32111 AN XY: 74216

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.460

Alfa AF: 0.501 Hom.: 2611

Bravo AF: 0.411

Asia WGS AF: 0.363 AC: 1262 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs10948516; hg19: chr6-49574354;