6-49612845-A-G

Variant names:

• chr6-49612845-A-G
• rs1480617
• NM_000324.3:c.808-311T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000324.3(RHAG):​c.808-311T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,922 control chromosomes in the GnomAD database, including 8,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8047 hom., cov: 31)
• Consequence: RHAG NM_000324.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• Rh deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• overhydrated hereditary stomatocytosis

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-49612845-A-G is Benign according to our data. Variant chr6-49612845-A-G is described in ClinVar as Benign. ClinVar VariationId is 1296822.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000324.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHAG	NM_000324.3	MANE Select	c.808-311T>C		intron	N/A	NP_000315.2	Q02094-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHAG	ENST00000371175.10	TSL:1 MANE Select	c.808-311T>C		intron	N/A	ENSP00000360217.4	Q02094-1
	RHAG	ENST00000646272.1		c.808-311T>C		intron	N/A	ENSP00000494337.1	A0A2R8YEH1
	RHAG	ENST00000646963.1		c.808-311T>C		intron	N/A	ENSP00000495337.1	Q9UHG9

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47979 AN: 151804 Hom.: 8041 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.310

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.316 AC: 48010 AN: 151922 Hom.: 8047 Cov.: 31 AF XY: 0.323 AC XY: 23983 AN XY: 74256

African (AFR) AF: 0.298 AC: 12363 AN: 41424

American (AMR) AF: 0.430 AC: 6562 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3466

East Asian (EAS) AF: 0.513 AC: 2642 AN: 5150

South Asian (SAS) AF: 0.350 AC: 1682 AN: 4806

European-Finnish (FIN) AF: 0.386 AC: 4076 AN: 10558

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18665 AN: 67960

Other (OTH) AF: 0.314 AC: 661 AN: 2106

Alfa AF: 0.292 Hom.: 25205

Bravo AF: 0.322

Asia WGS AF: 0.459 AC: 1594 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.64
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1480617; hg19: chr6-49580558;