chr1-25284610-G-T

Variant names:

• chr1-25284610-G-T
• rs199509194
• NM_016124.6:c.186G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282867.1(RHD):​c.-309G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,388,880 control chromosomes in the GnomAD database, including 943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.021 (425 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (518 hom.)
• Consequence: RHD NM_001282867.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062795877).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHD	NM_016124.6	c.186G>T	p.Leu62Phe	missense_variant	Exon 2 of 10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9	c.186G>T	p.Leu62Phe	missense_variant	Exon 2 of 10	1	NM_016124.6	ENSP00000331871.4

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 2770 AN: 134660 Hom.: 425 Cov.: 32

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00507

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00365

Gnomad NFE AF: 0.000316

Gnomad OTH AF: 0.0138

GnomAD2 exomes AF: 0.00559 AC: 1259 AN: 225376 AF XY: 0.00417

Gnomad AFR exome AF: 0.0678

Gnomad AMR exome AF: 0.00338

Gnomad ASJ exome AF: 0.00478

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000240

Gnomad OTH exome AF: 0.00457

GnomAD4 exome AF: 0.00237 AC: 2966 AN: 1254106 Hom.: 518 Cov.: 34 AF XY: 0.00206 AC XY: 1288 AN XY: 625558

Gnomad4 AFR exome AF: 0.0697 AC: 2257 AN: 32372

Gnomad4 AMR exome AF: 0.00403 AC: 172 AN: 42724

Gnomad4 ASJ exome AF: 0.00486 AC: 116 AN: 23864

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39552

Gnomad4 SAS exome AF: 0.000136 AC: 11 AN: 80970

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 47266

Gnomad4 NFE exome AF: 0.000102 AC: 95 AN: 928610

Gnomad4 Remaining exome AF: 0.00563 AC: 301 AN: 53456

GnomAD4 genome AF: 0.0206 AC: 2781 AN: 134774 Hom.: 425 Cov.: 32 AF XY: 0.0194 AC XY: 1285 AN XY: 66140

Gnomad4 AFR AF: 0.0659 AC: 0.0659375 AN: 0.0659375

Gnomad4 AMR AF: 0.0109 AC: 0.0108836 AN: 0.0108836

Gnomad4 ASJ AF: 0.00507 AC: 0.00507292 AN: 0.00507292

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000316 AC: 0.000315934 AN: 0.000315934

Gnomad4 OTH AF: 0.0136 AC: 0.0136411 AN: 0.0136411

Alfa AF: 0.00626 Hom.: 23

ESP6500AA AF: 0.0669 AC: 285

ESP6500EA AF: 0.000673 AC: 5

ExAC AF: 0.00656 AC: 729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.050
DANN	Benign	0.46
DEOGEN2	Benign	0.016	T;.;.;.;.;.;.;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.67	T;T;T;T;T;T;T;T;.
MetaRNN	Benign	0.0063	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.53	N;.;.;N;N;N;.;N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.0	N;.;.;N;N;N;N;N;N
REVEL	Benign	0.061
Sift	Benign	1.0	T;.;.;T;T;T;T;T;T
Sift4G	Benign	1.0	T;.;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.;.;.;B
Vest4		0.13
MutPred		0.53		Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);
MVP		0.055
MPC		0.095
ClinPred		0.0010	T
GERP RS		-5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.31
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199509194; hg19: chr1-25611101;