rs2269655

Variant names:

• chr1-175166468-C-A
• rs2269655
• NM_014656.3:c.-134+94G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-175166468-C-A
• chr1-175166468-C-T

Variant summary

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

The NM_014656.3(KIAA0040):​c.-134+94G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,190 control chromosomes in the GnomAD database, including 1,396 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 0.12 (1396 hom., cov: 32)
  • Exomes 𝑓: 0.067 (0 hom.)
• Consequence: KIAA0040 NM_014656.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0040	NM_014656.3	c.-134+94G>T		intron_variant	Intron 3 of 3	ENST00000423313.6	NP_055471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0040	ENST00000423313.6	c.-134+94G>T		intron_variant	Intron 3 of 3	1	NM_014656.3	ENSP00000462172.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17724 AN: 152042 Hom.: 1395 Cov.: 32

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.0667 AC: 2 AN: 30 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 22

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0500 AC: 1 AN: 20

Other (OTH) AF: 0.167 AC: 1 AN: 6

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.116 AC: 17722 AN: 152160 Hom.: 1396 Cov.: 32 AF XY: 0.119 AC XY: 8887 AN XY: 74390

African (AFR) AF: 0.0270 AC: 1121 AN: 41528

American (AMR) AF: 0.0917 AC: 1402 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3468

East Asian (EAS) AF: 0.311 AC: 1606 AN: 5164

South Asian (SAS) AF: 0.257 AC: 1239 AN: 4818

European-Finnish (FIN) AF: 0.157 AC: 1666 AN: 10578

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9805 AN: 67992

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.128 Hom.: 765

Bravo AF: 0.107

Asia WGS AF: 0.249 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.70
PhyloP100		-0.19
PromoterAI		-0.015	Neutral
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: rs2269655; hg19: chr1-175135604;