rs8076112

Positions:

• chr17-1708905-A-C
• chr17-1708905-A-G

Variant summary

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

The NM_001164407.2(TLCD2):​c.342+594T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,116 control chromosomes in the GnomAD database, including 2,445 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 0.16 (2445 hom., cov: 30)
• Consequence: TLCD2 NM_001164407.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

Genes affected

TLCD2 (HGNC:33522): (TLC domain containing 2) Involved in several processes, including membrane assembly; phospholipid homeostasis; and regulation of membrane lipid distribution. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLCD2	NM_001164407.2	c.342+594T>G		intron_variant		ENST00000330676.8	NP_001157879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLCD2	ENST00000330676.8	c.342+594T>G		intron_variant		2	NM_001164407.2	ENSP00000331965	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23700 AN: 151998 Hom.: 2448 Cov.: 30

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.156 AC: 23707 AN: 152116 Hom.: 2445 Cov.: 30 AF XY: 0.158 AC XY: 11763 AN XY: 74358

Gnomad4 AFR AF: 0.0699

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.157

Alfa AF: 0.169 Hom.: 3000

Bravo AF: 0.152

Asia WGS AF: 0.314 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.85

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: rs8076112; hg19: chr17-1612199;