chr5-176529270-A-C

Position:

• chr5-176529270-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014901.5(RNF44):​c.1236+18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 1,608,772 control chromosomes in the GnomAD database, including 623,582 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.90 (62523 hom., cov: 34)
  • Exomes 𝑓: 0.88 (561059 hom.)
• Consequence: RNF44 NM_014901.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.23

Genes affected

RNF44 (HGNC:19180): (ring finger protein 44) The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF44	NM_014901.5	c.1236+18T>G		intron_variant		ENST00000274811.9	NP_055716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF44	ENST00000274811.9	c.1236+18T>G		intron_variant		1	NM_014901.5	ENSP00000274811	P1
RNF44	ENST00000506378.1	c.519T>G	p.Ser173=	synonymous_variant	5/5	2		ENSP00000425253
RNF44	ENST00000515051.1	n.404T>G		non_coding_transcript_exon_variant	2/2	4
RNF44	ENST00000513029.5	c.*1034+18T>G		intron_variant, NMD_transcript_variant		2		ENSP00000427604

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137602 AN: 152200 Hom.: 62460 Cov.: 34

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.895

GnomAD3 exomes AF: 0.860 AC: 214793 AN: 249740 Hom.: 93031 AF XY: 0.853 AC XY: 115408 AN XY: 135308

Gnomad AFR exome AF: 0.974

Gnomad AMR exome AF: 0.851

Gnomad ASJ exome AF: 0.862

Gnomad EAS exome AF: 0.777

Gnomad SAS exome AF: 0.709

Gnomad FIN exome AF: 0.922

Gnomad NFE exome AF: 0.889

Gnomad OTH exome AF: 0.869

GnomAD4 exome AF: 0.876 AC: 1276126 AN: 1456454 Hom.: 561059 Cov.: 32 AF XY: 0.871 AC XY: 631490 AN XY: 724848

Gnomad4 AFR exome AF: 0.973

Gnomad4 AMR exome AF: 0.853

Gnomad4 ASJ exome AF: 0.863

Gnomad4 EAS exome AF: 0.777

Gnomad4 SAS exome AF: 0.717

Gnomad4 FIN exome AF: 0.920

Gnomad4 NFE exome AF: 0.889

Gnomad4 OTH exome AF: 0.873

GnomAD4 genome AF: 0.904 AC: 137727 AN: 152318 Hom.: 62523 Cov.: 34 AF XY: 0.901 AC XY: 67078 AN XY: 74472

Gnomad4 AFR AF: 0.973

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.930

Gnomad4 NFE AF: 0.890

Gnomad4 OTH AF: 0.895

Alfa AF: 0.881 Hom.: 48927

Bravo AF: 0.907

EpiCase AF: 0.888

EpiControl AF: 0.888

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.014
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs890835; hg19: chr5-175956271;