17-74356708-C-T

Variant names:

• chr17-74356708-C-T
• rs774047988
• NM_001080466.2:c.1386G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001080466.2(BTBD17):​c.1386G>A​(p.Leu462Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,440,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L462L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: BTBD17 NM_001080466.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796
• Publications: 0 publications found

Genes affected

BTBD17 (HGNC:33758): (BTB domain containing 17) Predicted to be involved in negative regulation of viral genome replication and response to virus. Predicted to be located in plasma membrane. Predicted to colocalize with cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=-0.796 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080466.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD17	NM_001080466.2	MANE Select	c.1386G>A	p.Leu462Leu	synonymous	Exon 3 of 3	NP_001073935.1	A6NE02

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD17	ENST00000375366.4	TSL:1 MANE Select	c.1386G>A	p.Leu462Leu	synonymous	Exon 3 of 3	ENSP00000364515.3	A6NE02

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000129 AC: 3 AN: 232374 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000962

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000416 AC: 6 AN: 1440902 Hom.: 0 Cov.: 33 AF XY: 0.00000419 AC XY: 3 AN XY: 715992

African (AFR) AF: 0.00 AC: 0 AN: 31936

American (AMR) AF: 0.0000713 AC: 3 AN: 42062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25648

East Asian (EAS) AF: 0.0000801 AC: 3 AN: 37444

South Asian (SAS) AF: 0.00 AC: 0 AN: 82832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102440

Other (OTH) AF: 0.00 AC: 0 AN: 59608

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	3.8
DANN	Benign	0.95
PhyloP100		-0.80

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: rs774047988; hg19: chr17-72352847; COSMIC: COSV100945434; COSMIC: COSV100945434;