NM_016124.6:c.744C>T

Variant names:

• chr1-25301629-C-T
• rs1053362
• NM_016124.6:c.744C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Very_Strong BP7 BS2_Supporting

The NM_016124.6(RHD):​c.744C>T​(p.Ser248Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000848 in 1,379,912 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (62 hom., cov: 21)
  • Exomes 𝑓: 0.00060 (137 hom.)
• Consequence: RHD NM_016124.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.234
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-25301629-C-T is Benign according to our data. Variant chr1-25301629-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 242595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.234 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 62 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.744C>T	p.Ser248Ser	synonymous	Exon 5 of 10	NP_057208.3
	RHD	NM_001282871.2		c.744C>T	p.Ser248Ser	synonymous	Exon 5 of 9	NP_001269800.1
	RHD	NM_001282870.1		c.744C>T	p.Ser248Ser	synonymous	Exon 5 of 9	NP_001269799.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHD	ENST00000328664.9	TSL:1 MANE Select	c.744C>T	p.Ser248Ser	synonymous	Exon 5 of 10	ENSP00000331871.4
	RHD	ENST00000342055.9	TSL:1	c.744C>T	p.Ser248Ser	synonymous	Exon 5 of 9	ENSP00000339577.5
	RHD	ENST00000568195.5	TSL:1	c.744C>T	p.Ser248Ser	synonymous	Exon 5 of 9	ENSP00000456966.1

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 411 AN: 132948 Hom.: 59 Cov.: 21

Gnomad AFR AF: 0.00979

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000713

Gnomad OTH AF: 0.00161

GnomAD2 exomes AF: 0.00106 AC: 238 AN: 225162 AF XY: 0.000734

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.00160

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000599

Gnomad FIN exome AF: 0.0000524

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000549

GnomAD4 exome AF: 0.000595 AC: 742 AN: 1246848 Hom.: 137 Cov.: 31 AF XY: 0.000523 AC XY: 325 AN XY: 621944

African (AFR) AF: 0.0125 AC: 397 AN: 31850

American (AMR) AF: 0.00152 AC: 65 AN: 42642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23794

East Asian (EAS) AF: 0.00147 AC: 58 AN: 39534

South Asian (SAS) AF: 0.000223 AC: 18 AN: 80540

European-Finnish (FIN) AF: 0.0000213 AC: 1 AN: 47046

Middle Eastern (MID) AF: 0.00133 AC: 7 AN: 5254

European-Non Finnish (NFE) AF: 0.000117 AC: 108 AN: 922996

Other (OTH) AF: 0.00165 AC: 88 AN: 53192

GnomAD4 genome AF: 0.00322 AC: 428 AN: 133064 Hom.: 62 Cov.: 21 AF XY: 0.00317 AC XY: 207 AN XY: 65206

African (AFR) AF: 0.0102 AC: 393 AN: 38648

American (AMR) AF: 0.00151 AC: 21 AN: 13864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3146

East Asian (EAS) AF: 0.00117 AC: 6 AN: 5126

South Asian (SAS) AF: 0.000227 AC: 1 AN: 4408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.0000713 AC: 4 AN: 56120

Other (OTH) AF: 0.00159 AC: 3 AN: 1884

Alfa AF: 0.0000821 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.5
DANN	Benign	0.47
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1053362; hg19: chr1-25628120;