chr1-175166693-G-A

Variant names:

• chr1-175166693-G-A
• rs2861158
• NM_014656.3:c.-265C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014656.3(KIAA0040):​c.-265C>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 0.224 in 152,038 control chromosomes in the GnomAD database, including 4,929 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 0.22 (4929 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: KIAA0040 NM_014656.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 10 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 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.-265C>T		5_prime_UTR	Exon 3 of 4	NP_055471.2
	KIAA0040	NM_001162893.2		c.-265C>T		5_prime_UTR	Exon 4 of 5	NP_001156365.1
	KIAA0040	NM_001162894.2		c.-265C>T		5_prime_UTR	Exon 3 of 4	NP_001156366.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0040	ENST00000423313.6	TSL:1 MANE Select	c.-265C>T		5_prime_UTR	Exon 3 of 4	ENSP00000462172.1
	KIAA0040	ENST00000444639.5	TSL:1	c.-265C>T		5_prime_UTR	Exon 3 of 4	ENSP00000463734.1
	KIAA0040	ENST00000545251.6	TSL:1	c.-265C>T		5_prime_UTR	Exon 2 of 3	ENSP00000464040.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34042 AN: 151884 Hom.: 4921 Cov.: 32

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.167 AC: 6 AN: 36 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 4 AN XY: 24

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.125 AC: 2 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 4 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.224 AC: 34054 AN: 152002 Hom.: 4929 Cov.: 32 AF XY: 0.226 AC XY: 16773 AN XY: 74282

African (AFR) AF: 0.0529 AC: 2198 AN: 41514

American (AMR) AF: 0.400 AC: 6102 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3466

East Asian (EAS) AF: 0.314 AC: 1620 AN: 5154

South Asian (SAS) AF: 0.308 AC: 1480 AN: 4802

European-Finnish (FIN) AF: 0.184 AC: 1944 AN: 10558

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18406 AN: 67948

Other (OTH) AF: 0.269 AC: 566 AN: 2106

Alfa AF: 0.267 Hom.: 16606

Bravo AF: 0.236

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		-0.065
PromoterAI		-0.068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 44

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2861158; hg19: chr1-175135829;