chr1-175160810-C-T

Variant names:

• chr1-175160810-C-T
• rs2072035
• NM_014656.3:c.204G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_014656.3(KIAA0040):​c.204G>A​(p.Lys68Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.61 (13995 hom., cov: 25)
  • Exomes 𝑓: 0.56 (89855 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIAA0040 NM_014656.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 15 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.514 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0040	NM_014656.3	c.204G>A	p.Lys68Lys	synonymous_variant	Exon 4 of 4	ENST00000423313.6	NP_055471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0040	ENST00000423313.6	c.204G>A	p.Lys68Lys	synonymous_variant	Exon 4 of 4	1	NM_014656.3	ENSP00000462172.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 64063 AN: 105202 Hom.: 13961 Cov.: 25

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.624

GnomAD2 exomes AF: 0.457 AC: 69489 AN: 152216 AF XY: 0.449

Gnomad AFR exome AF: 0.499

Gnomad AMR exome AF: 0.642

Gnomad ASJ exome AF: 0.542

Gnomad EAS exome AF: 0.542

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.443

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.556 AC: 509008 AN: 916132 Hom.: 89855 Cov.: 40 AF XY: 0.556 AC XY: 252241 AN XY: 453948

African (AFR) AF: 0.620 AC: 14791 AN: 23874

American (AMR) AF: 0.710 AC: 21549 AN: 30360

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 12921 AN: 20252

East Asian (EAS) AF: 0.589 AC: 18316 AN: 31118

South Asian (SAS) AF: 0.562 AC: 34076 AN: 60626

European-Finnish (FIN) AF: 0.569 AC: 17460 AN: 30682

Middle Eastern (MID) AF: 0.566 AC: 2142 AN: 3782

European-Non Finnish (NFE) AF: 0.541 AC: 365372 AN: 675878

Other (OTH) AF: 0.566 AC: 22381 AN: 39560

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.609 AC: 64154 AN: 105318 Hom.: 13995 Cov.: 25 AF XY: 0.610 AC XY: 31565 AN XY: 51760

African (AFR) AF: 0.639 AC: 19597 AN: 30676

American (AMR) AF: 0.673 AC: 8048 AN: 11960

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 1860 AN: 2816

East Asian (EAS) AF: 0.603 AC: 2748 AN: 4560

South Asian (SAS) AF: 0.578 AC: 2165 AN: 3744

European-Finnish (FIN) AF: 0.573 AC: 3765 AN: 6576

Middle Eastern (MID) AF: 0.650 AC: 134 AN: 206

European-Non Finnish (NFE) AF: 0.574 AC: 24467 AN: 42596

Other (OTH) AF: 0.624 AC: 923 AN: 1478

Alfa AF: 0.397 Hom.: 1970

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		0.51
Mutation Taster		=90/10	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: rs2072035; hg19: chr1-175129946; COSMIC: COSV70593739; COSMIC: COSV70593739;