1-95226754-G-A

Variant names:

• chr1-95226754-G-A
• rs1414896
• ENST00000604534.5:c.474-4148G>A

Variant summary

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

The ENST00000604534.5(TLCD4-RWDD3):​c.474-4148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,000 control chromosomes in the GnomAD database, including 20,951 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 0.51 (20951 hom., cov: 32)
• Consequence: TLCD4-RWDD3 ENST00000604534.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 14 publications found

Genes affected

TLCD4-RWDD3 (HGNC:49388): (TLCD4-RWDD3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TMEM56 (transmembrane protein 56) and RWDD3 (RWD domain containing 3) genes on chromosome 1. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product, but it contains a distinct C-terminus due to frameshifts versus the downstream gene coding sequence. [provided by RefSeq, Dec 2010]

RWDD3-DT (HGNC:55839): (RWDD3 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD4-RWDD3	NM_001199691.1	c.474-4148G>A		intron_variant	Intron 6 of 7		NP_001186620.1
RWDD3-DT	NR_125948.1	n.284-4923C>T		intron_variant	Intron 1 of 4
RWDD3-DT	NR_125949.1	n.284-4923C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLCD4-RWDD3	ENST00000604534.5	c.474-4148G>A		intron_variant	Intron 6 of 7	2		ENSP00000475025.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77282 AN: 151880 Hom.: 20951 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.544

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.509 AC: 77298 AN: 152000 Hom.: 20951 Cov.: 32 AF XY: 0.507 AC XY: 37669 AN XY: 74296

African (AFR) AF: 0.317 AC: 13160 AN: 41452

American (AMR) AF: 0.558 AC: 8525 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2259 AN: 3470

East Asian (EAS) AF: 0.332 AC: 1716 AN: 5166

South Asian (SAS) AF: 0.651 AC: 3140 AN: 4822

European-Finnish (FIN) AF: 0.495 AC: 5234 AN: 10564

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41378 AN: 67942

Other (OTH) AF: 0.544 AC: 1146 AN: 2106

Alfa AF: 0.580 Hom.: 93803

Bravo AF: 0.497

Asia WGS AF: 0.492 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.75
PhyloP100		-0.063
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: rs1414896; hg19: chr1-95692310;