6-49606928-C-T

Variant names:

• chr6-49606928-C-T
• rs150091685
• NM_000324.3:c.1139-7G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000324.3(RHAG):​c.1139-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 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, intron
• Scores: Splicing: ADA: 0.00003437
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.870

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR,BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHAG	NM_000324.3	c.1139-7G>A		splice_region_variant, intron_variant	Intron 8 of 9	ENST00000371175.10	NP_000315.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHAG	ENST00000371175.10	c.1139-7G>A		splice_region_variant, intron_variant	Intron 8 of 9	1	NM_000324.3	ENSP00000360217.4
RHAG	ENST00000646272.1	c.1139-7G>A		splice_region_variant, intron_variant	Intron 8 of 9			ENSP00000494337.1
RHAG	ENST00000646963.1	c.1138+222G>A		intron_variant	Intron 8 of 8			ENSP00000495337.1
RHAG	ENST00000646939.1	c.1017-7G>A		splice_region_variant, intron_variant	Intron 7 of 8			ENSP00000494709.1

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 241 AN: 152044 Hom.: 2 Cov.: 33

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

GnomAD2 exomes AF: 0.00185 AC: 465 AN: 250744 AF XY: 0.00187

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 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.: 7 Cov.: 28 AF XY: 0.00233 AC XY: 1682 AN XY: 722030

Gnomad4 AFR exome AF: 0.000784 AC: 26 AN: 33178

Gnomad4 AMR exome AF: 0.000694 AC: 31 AN: 44654

Gnomad4 ASJ exome AF: 0.000460 AC: 12 AN: 26074

Gnomad4 EAS exome AF: 0.00101 AC: 40 AN: 39628

Gnomad4 SAS exome AF: 0.000244 AC: 21 AN: 85996

Gnomad4 FIN exome AF: 0.00259 AC: 138 AN: 53362

Gnomad4 NFE exome AF: 0.00280 AC: 3080 AN: 1101160

Gnomad4 Remaining exome AF: 0.00207 AC: 124 AN: 59950

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152162 Hom.: 2 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74376

Gnomad4 AFR AF: 0.000771 AC: 0.000770899 AN: 0.000770899

Gnomad4 AMR AF: 0.000785 AC: 0.000784929 AN: 0.000784929

Gnomad4 ASJ AF: 0.000288 AC: 0.000288351 AN: 0.000288351

Gnomad4 EAS AF: 0.00154 AC: 0.00154381 AN: 0.00154381

Gnomad4 SAS AF: 0.000416 AC: 0.000416146 AN: 0.000416146

Gnomad4 FIN AF: 0.00208 AC: 0.00207782 AN: 0.00207782

Gnomad4 NFE AF: 0.00240 AC: 0.00239699 AN: 0.00239699

Gnomad4 OTH AF: 0.000473 AC: 0.000473485 AN: 0.000473485

Alfa AF: 0.00194 Hom.: 0

Bravo AF: 0.00146

EpiCase AF: 0.00338

EpiControl AF: 0.00427

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.28
DANN	Benign	0.62
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs150091685; hg19: chr6-49574641; COSMIC: COSV57703569;