rs1031261

chr2-32640454-G-C

Variant summary

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

The NM_017735.5(TTC27):c.537+44G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,592,104 control chromosomes in the GnomAD database, including 18,220 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 0.14 (1615 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16605 hom.)
• Consequence: TTC27 NM_017735.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

Genes affected

TTC27 (HGNC:25986): (tetratricopeptide repeat domain 27)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC27	NM_017735.5	c.537+44G>C		intron_variant		ENST00000317907.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC27	ENST00000317907.9	c.537+44G>C		intron_variant		1	NM_017735.5	P1
TTC27	ENST00000454690.1	c.88+12074G>C		intron_variant, NMD_transcript_variant		3
TTC27	ENST00000647819.1	c.537+44G>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20639 AN: 151936 Hom.: 1612 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.173 AC: 41598 AN: 240546 Hom.: 4392 AF XY: 0.181 AC XY: 23529 AN XY: 130314

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.0974

Gnomad EAS exome AF: 0.306

Gnomad SAS exome AF: 0.346

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.139 AC: 200085 AN: 1440050 Hom.: 16605 Cov.: 27 AF XY: 0.145 AC XY: 103950 AN XY: 716314

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.0965

Gnomad4 EAS exome AF: 0.278

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.136 AC: 20660 AN: 152054 Hom.: 1615 Cov.: 32 AF XY: 0.140 AC XY: 10410 AN XY: 74334

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.128

Alfa AF: 0.132 Hom.: 937

Bravo AF: 0.131

Asia WGS AF: 0.333 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.3
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1031261; hg19: chr2-32865521; COSMIC: COSV58648669; COSMIC: COSV58648669;