NM_014656.3:c.-309-1503C>A

Variant names:

• chr1-175168240-G-T
• rs760486
• NM_014656.3:c.-309-1503C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014656.3(KIAA0040):​c.-309-1503C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,970 control chromosomes in the GnomAD database, including 10,215 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 0.35 (10215 hom., cov: 32)
• Consequence: KIAA0040 NM_014656.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854
• Publications: 3 publications found

Genes affected

KIAA0040 (HGNC:28950): (KIAA0040) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014656.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0040	NM_014656.3	MANE Select	c.-309-1503C>A		intron	N/A	NP_055471.2
	KIAA0040	NM_001162893.2		c.-309-1503C>A		intron	N/A	NP_001156365.1
	KIAA0040	NM_001162894.2		c.-309-1503C>A		intron	N/A	NP_001156366.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0040	ENST00000423313.6	TSL:1 MANE Select	c.-309-1503C>A		intron	N/A	ENSP00000462172.1
	KIAA0040	ENST00000444639.5	TSL:1	c.-309-1503C>A		intron	N/A	ENSP00000463734.1
	KIAA0040	ENST00000545251.6	TSL:1	c.-309-1503C>A		intron	N/A	ENSP00000464040.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53474 AN: 151850 Hom.: 10198 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.352 AC: 53529 AN: 151970 Hom.: 10215 Cov.: 32 AF XY: 0.358 AC XY: 26574 AN XY: 74290

African (AFR) AF: 0.220 AC: 9116 AN: 41416

American (AMR) AF: 0.510 AC: 7779 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1834 AN: 3472

East Asian (EAS) AF: 0.542 AC: 2801 AN: 5166

South Asian (SAS) AF: 0.440 AC: 2119 AN: 4820

European-Finnish (FIN) AF: 0.359 AC: 3789 AN: 10550

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24701 AN: 67962

Other (OTH) AF: 0.385 AC: 814 AN: 2112

Alfa AF: 0.342 Hom.: 4143

Bravo AF: 0.363

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.32
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs760486; hg19: chr1-175137376;