NM_016124.6:c.609G>A

Variant names:

• chr1-25301068-G-A
• rs114032679
• NM_016124.6:c.609G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_016124.6(RHD):​c.609G>A​(p.Thr203Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,376,838 control chromosomes in the GnomAD database, including 599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (264 hom., cov: 21)
  • Exomes 𝑓: 0.0015 (335 hom.)
• Consequence: RHD NM_016124.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.85
• Publications: 4 publications found

Genes affected

RHD (HGNC:10009): (Rh blood group D antigen) The Rh blood group system is the second most clinically significant of the blood groups, second only to ABO. It is also the most polymorphic of the blood groups, with variations due to deletions, gene conversions, and missense mutations. The Rh blood group includes this gene, which encodes the RhD protein, and a second gene that encodes both the RhC and RhE antigens on a single polypeptide. The two genes, and a third unrelated gene, are found in a cluster on chromosome 1. The classification of Rh-positive and Rh-negative individuals is determined by the presence or absence of the highly immunogenic RhD protein on the surface of erythrocytes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-25301068-G-A is Benign according to our data. Variant chr1-25301068-G-A is described in ClinVar as Benign. ClinVar VariationId is 780764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.85 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0132 (1721/130574) while in subpopulation AFR AF = 0.0424 (1608/37946). AF 95% confidence interval is 0.0407. There are 264 homozygotes in GnomAd4. There are 783 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 264 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016124.6. 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
	RHD	NM_016124.6	MANE Select	c.609G>A	p.Thr203Thr	synonymous	Exon 4 of 10	NP_057208.3
	RHD	NM_001282871.2		c.609G>A	p.Thr203Thr	synonymous	Exon 4 of 9	NP_001269800.1	Q02161-4
	RHD	NM_001282870.1		c.609G>A	p.Thr203Thr	synonymous	Exon 4 of 9	NP_001269799.1	Q5XLT0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHD	ENST00000328664.9	TSL:1 MANE Select	c.609G>A	p.Thr203Thr	synonymous	Exon 4 of 10	ENSP00000331871.4	Q02161-1
	RHD	ENST00000342055.9	TSL:1	c.609G>A	p.Thr203Thr	synonymous	Exon 4 of 9	ENSP00000339577.5	Q02161-4
	RHD	ENST00000568195.5	TSL:1	c.609G>A	p.Thr203Thr	synonymous	Exon 4 of 9	ENSP00000456966.1	H3BT10

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 1718 AN: 130458 Hom.: 264 Cov.: 21

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00666

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000720

Gnomad OTH AF: 0.0111

GnomAD2 exomes AF: 0.00343 AC: 771 AN: 224652 AF XY: 0.00275

Gnomad AFR exome AF: 0.0444

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000525

Gnomad OTH exome AF: 0.00110

GnomAD4 exome AF: 0.00147 AC: 1837 AN: 1246264 Hom.: 335 Cov.: 31 AF XY: 0.00129 AC XY: 804 AN XY: 621574

African (AFR) AF: 0.0460 AC: 1470 AN: 31938

American (AMR) AF: 0.00293 AC: 125 AN: 42612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23772

East Asian (EAS) AF: 0.00 AC: 0 AN: 39532

South Asian (SAS) AF: 0.000199 AC: 16 AN: 80522

European-Finnish (FIN) AF: 0.0000426 AC: 2 AN: 46994

Middle Eastern (MID) AF: 0.00240 AC: 12 AN: 4998

European-Non Finnish (NFE) AF: 0.0000260 AC: 24 AN: 922748

Other (OTH) AF: 0.00354 AC: 188 AN: 53148

GnomAD4 genome AF: 0.0132 AC: 1721 AN: 130574 Hom.: 264 Cov.: 21 AF XY: 0.0123 AC XY: 783 AN XY: 63804

African (AFR) AF: 0.0424 AC: 1608 AN: 37946

American (AMR) AF: 0.00664 AC: 89 AN: 13394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3110

East Asian (EAS) AF: 0.00 AC: 0 AN: 5078

South Asian (SAS) AF: 0.00 AC: 0 AN: 4312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.0000721 AC: 4 AN: 55516

Other (OTH) AF: 0.0110 AC: 20 AN: 1818

Alfa AF: 0.00541 Hom.: 25

Asia WGS AF: 0.00178 AC: 6 AN: 3390

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.58
DANN	Benign	0.64
PhyloP100		-1.9
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: rs114032679; hg19: chr1-25627559;