1-175165541-A-G

Variant summary

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

The NM_014656.3(KIAA0040):c.-134+1021T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,082 control chromosomes in the GnomAD database, including 25,002 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 0.57 (25002 hom., cov: 32)
• Consequence: KIAA0040 NM_014656.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

Genes affected

KIAA0040 (HGNC:28950): (KIAA0040) Predicted to be integral component of 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0040	NM_014656.3	c.-134+1021T>C		intron_variant		ENST00000423313.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0040	ENST00000423313.6	c.-134+1021T>C		intron_variant		1	NM_014656.3	P1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86346 AN: 151964 Hom.: 24965 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.568 AC: 86443 AN: 152082 Hom.: 25002 Cov.: 32 AF XY: 0.574 AC XY: 42649 AN XY: 74358

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.583

Alfa AF: 0.540 Hom.: 12755

Bravo AF: 0.582

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.1
Dann	Benign	0.68

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: rs10489326; hg19: chr1-175134677; COSMIC: COSV70594424;