4-2690977-C-T

Variant summary

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

The NM_001366318.2(FAM193A):c.2803+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00623 in 1,606,410 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (53 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (70 hom.)
• Consequence: FAM193A NM_001366318.2 splice_region, intron
• Scores: Splicing: ADA: 0.00001573
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.415

Genes affected

FAM193A (HGNC:16822): (family with sequence similarity 193 member A)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-2690977-C-T is Benign according to our data. Variant chr4-2690977-C-T is described in ClinVar as [Benign]. Clinvar id is 773678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0169 (2572/152252) while in subpopulation AFR AF= 0.0487 (2024/41528). AF 95% confidence interval is 0.047. There are 53 homozygotes in gnomad4. There are 1279 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 53 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM193A	NM_001366318.2	c.2803+7C>T		splice_region_variant, intron_variant		ENST00000637812.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM193A	ENST00000637812.2	c.2803+7C>T		splice_region_variant, intron_variant		5	NM_001366318.2	A2

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2565 AN: 152134 Hom.: 53 Cov.: 33

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.00830

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00304

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00803 AC: 1983 AN: 247044 Hom.: 24 AF XY: 0.00708 AC XY: 945 AN XY: 133552

Gnomad AFR exome AF: 0.0493

Gnomad AMR exome AF: 0.00569

Gnomad ASJ exome AF: 0.000307

Gnomad EAS exome AF: 0.0182

Gnomad SAS exome AF: 0.00702

Gnomad FIN exome AF: 0.00186

Gnomad NFE exome AF: 0.00337

Gnomad OTH exome AF: 0.00551

GnomAD4 exome AF: 0.00511 AC: 7435 AN: 1454158 Hom.: 70 Cov.: 31 AF XY: 0.00506 AC XY: 3657 AN XY: 722250

Gnomad4 AFR exome AF: 0.0510

Gnomad4 AMR exome AF: 0.00638

Gnomad4 ASJ exome AF: 0.000309

Gnomad4 EAS exome AF: 0.0146

Gnomad4 SAS exome AF: 0.00686

Gnomad4 FIN exome AF: 0.00187

Gnomad4 NFE exome AF: 0.00337

Gnomad4 OTH exome AF: 0.00717

GnomAD4 genome AF: 0.0169 AC: 2572 AN: 152252 Hom.: 53 Cov.: 33 AF XY: 0.0172 AC XY: 1279 AN XY: 74444

Gnomad4 AFR AF: 0.0487

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.00831

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.00304

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00906 Hom.: 14

Bravo AF: 0.0193

EpiCase AF: 0.00344

EpiControl AF: 0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	10
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.020		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: rs79752154; hg19: chr4-2692704;