rs4648356

Variant names:

• chr1-2792599-C-A
• rs4648356
• NM_001242672.3:c.785-2253G>T

Variant summary

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

The NM_001242672.3(TTC34):​c.785-2253G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,994 control chromosomes in the GnomAD database, including 11,960 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 0.39 (11960 hom., cov: 31)
• Consequence: TTC34 NM_001242672.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 59 publications found

Genes affected

TTC34 (HGNC:34297): (tetratricopeptide repeat domain 34)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC34	NM_001242672.3	c.785-2253G>T		intron_variant	Intron 2 of 8	ENST00000401095.9	NP_001229601.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC34	ENST00000401095.9	c.785-2253G>T		intron_variant	Intron 2 of 8	5	NM_001242672.3	ENSP00000383873.4

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58759 AN: 151878 Hom.: 11943 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.387 AC: 58802 AN: 151994 Hom.: 11960 Cov.: 31 AF XY: 0.392 AC XY: 29119 AN XY: 74274

African (AFR) AF: 0.476 AC: 19744 AN: 41438

American (AMR) AF: 0.424 AC: 6473 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2819 AN: 5150

South Asian (SAS) AF: 0.487 AC: 2350 AN: 4824

European-Finnish (FIN) AF: 0.361 AC: 3810 AN: 10558

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21537 AN: 67960

Other (OTH) AF: 0.359 AC: 756 AN: 2106

Alfa AF: 0.347 Hom.: 19160

Bravo AF: 0.391

Asia WGS AF: 0.573 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.32
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4648356; hg19: chr1-2709164;