1-25290800-T-C

Variant summary

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

The NM_016124.6(RHD):c.486+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,374,792 control chromosomes in the GnomAD database, including 627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (257 hom., cov: 20)
  • Exomes 𝑓: 0.0017 (370 hom.)
• Consequence: RHD NM_016124.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.63

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 1-25290800-T-C is Benign according to our data. Variant chr1-25290800-T-C is described in ClinVar as [Benign]. Clinvar id is 791783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHD	NM_016124.6	c.486+9T>C		intron_variant		ENST00000328664.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHD	ENST00000328664.9	c.486+9T>C		intron_variant		1	NM_016124.6	P1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2320 AN: 129046 Hom.: 257 Cov.: 20

Gnomad AFR AF: 0.0568

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00928

Gnomad ASJ AF: 0.00680

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000243

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00382

Gnomad NFE AF: 0.000292

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00514 AC: 1155 AN: 224800 Hom.: 209 AF XY: 0.00388 AC XY: 470 AN XY: 121112

Gnomad AFR exome AF: 0.0600

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00653

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000210

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000251

Gnomad OTH exome AF: 0.00457

GnomAD4 exome AF: 0.00166 AC: 2070 AN: 1245626 Hom.: 370 Cov.: 31 AF XY: 0.00144 AC XY: 895 AN XY: 621312

Gnomad4 AFR exome AF: 0.0470

Gnomad4 AMR exome AF: 0.00362

Gnomad4 ASJ exome AF: 0.00556

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000149

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000856

Gnomad4 OTH exome AF: 0.00415

GnomAD4 genome AF: 0.0181 AC: 2332 AN: 129166 Hom.: 257 Cov.: 20 AF XY: 0.0170 AC XY: 1069 AN XY: 63026

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.00927

Gnomad4 ASJ AF: 0.00680

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000292

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0139 Hom.: 24

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

Invitae

Aug 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0050
Dann	Benign	0.34

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: rs113795383; hg19: chr1-25617291;