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GeneBe

1-25290671-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016124.6(RHD):c.366G>A(p.Ser122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,378,290 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 2 hom., cov: 20)
Exomes 𝑓: 0.000031 ( 12 hom. )

Consequence

RHD
NM_016124.6 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.68
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-25290671-G-A is Benign according to our data. Variant chr1-25290671-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 739638.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.67 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 BG gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RHDNM_016124.6 linkuse as main transcriptc.366G>A p.Ser122= synonymous_variant 3/10 ENST00000328664.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RHDENST00000328664.9 linkuse as main transcriptc.366G>A p.Ser122= synonymous_variant 3/101 NM_016124.6 P1Q02161-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000459
AC:
6
AN:
130736
Hom.:
2
Cov.:
20
show subpopulations
Gnomad AFR
AF:
0.0000261
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000195
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000724
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000533
AC:
12
AN:
224982
Hom.:
3
AF XY:
0.0000743
AC XY:
9
AN XY:
121170
show subpopulations
Gnomad AFR exome
AF:
0.0000637
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.000175
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000419
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000313
AC:
39
AN:
1247436
Hom.:
12
Cov.:
31
AF XY:
0.0000466
AC XY:
29
AN XY:
622162
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000137
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000238
Gnomad4 OTH exome
AF:
0.0000563
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000459
AC:
6
AN:
130854
Hom.:
2
Cov.:
20
AF XY:
0.0000469
AC XY:
3
AN XY:
63940
show subpopulations
Gnomad4 AFR
AF:
0.0000260
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000195
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000724
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeApr 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
0.37
Dann
Benign
0.74
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs188168550; hg19: chr1-25617162; COSMIC: COSV100155245; COSMIC: COSV100155245; API