rs1057239

Positions:

• chr1-175161068-G-A

Variant summary

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

The NM_014656.3(KIAA0040):​c.-55C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,479,164 control chromosomes in the GnomAD database, including 142,773 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 0.41 (12917 hom., cov: 32)
  • Exomes 𝑓: 0.44 (129856 hom.)
• Consequence: KIAA0040 NM_014656.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0040	NM_014656.3	c.-55C>T		5_prime_UTR_variant	4/4	ENST00000423313.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0040	ENST00000423313.6	c.-55C>T		5_prime_UTR_variant	4/4	1	NM_014656.3	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61626 AN: 151882 Hom.: 12920 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.435 AC: 577592 AN: 1327162 Hom.: 129856 Cov.: 24 AF XY: 0.430 AC XY: 279789 AN XY: 650412

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.131

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.403

GnomAD4 genome AF: 0.406 AC: 61647 AN: 152002 Hom.: 12917 Cov.: 32 AF XY: 0.402 AC XY: 29864 AN XY: 74298

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.393

Alfa AF: 0.422 Hom.: 24499

Bravo AF: 0.390

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.76

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: rs1057239; hg19: chr1-175130204; COSMIC: COSV70594026;