15-59373198-C-T

Position:

• chr15-59373198-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000560394.5(FAM81A):​c.-161+107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 152,168 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (84 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM81A ENST00000560394.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.963

Genes affected

FAM81A (HGNC:28379): (family with sequence similarity 81 member A)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 15-59373198-C-T is Benign according to our data. Variant chr15-59373198-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1218505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0278 (4235/152168) while in subpopulation NFE AF= 0.0408 (2775/67994). AF 95% confidence interval is 0.0395. There are 84 homozygotes in gnomad4. There are 2021 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 84 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.59373198C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM81A	ENST00000560394.5	c.-161+107C>T		intron_variant		4		ENSP00000452962.1
FAM81A	ENST00000558348.5	c.-161+419C>T		intron_variant		4		ENSP00000453918.1

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4238 AN: 152050 Hom.: 84 Cov.: 31

Gnomad AFR AF: 0.00681

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0156

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0339

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0278 AC: 4235 AN: 152168 Hom.: 84 Cov.: 31 AF XY: 0.0272 AC XY: 2021 AN XY: 74404

Gnomad4 AFR AF: 0.00677

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.0859

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0154

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.0408

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0377 Hom.: 22

Bravo AF: 0.0286

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 22, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56016418; hg19: chr15-59665397; COSMIC: COSV55690801;