15-59372979-A-C

Position:

• chr15-59372979-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000558348.5(FAM81A):​c.-161+200A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00572 in 156,500 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (8 hom., cov: 31)
  • Exomes 𝑓: 0.0024 (0 hom.)
• Consequence: FAM81A ENST00000558348.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.104

Genes affected

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

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 15-59372979-A-C is Benign according to our data. Variant chr15-59372979-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1706778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00581 (885/152300) while in subpopulation AFR AF= 0.0173 (719/41564). AF 95% confidence interval is 0.0163. There are 8 homozygotes in gnomad4. There are 420 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.59372979A>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM81A	ENST00000558348.5	c.-161+200A>C		intron_variant		4		ENSP00000453918.1
FAM81A	ENST00000560394.5	c.-273A>C		upstream_gene_variant		4		ENSP00000452962.1

Frequencies

GnomAD3 genomes AF: 0.00582 AC: 886 AN: 152182 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00238 AC: 10 AN: 4200 Hom.: 0 Cov.: 0 AF XY: 0.00226 AC XY: 5 AN XY: 2212

Gnomad4 AFR exome AF: 0.0242

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0352

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00847

GnomAD4 genome AF: 0.00581 AC: 885 AN: 152300 Hom.: 8 Cov.: 31 AF XY: 0.00564 AC XY: 420 AN XY: 74480

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00376 Hom.: 2

Bravo AF: 0.00610

Asia WGS AF: 0.00144 AC: 5 AN: 3478

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

Nov 29, 2019

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111309933; hg19: chr15-59665178;