1-175187292-G-C

Variant names:

• chr1-175187292-G-C
• rs3766685
• NM_014656.3:c.-384+5348C>G

Variant summary

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

The NM_014656.3(KIAA0040):​c.-384+5348C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,006 control chromosomes in the GnomAD database, including 18,763 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 0.49 (18763 hom., cov: 32)
• Consequence: KIAA0040 NM_014656.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 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.-384+5348C>G		intron	N/A	NP_055471.2
	KIAA0040	NM_001162893.2		c.-384+5348C>G		intron	N/A	NP_001156365.1
	KIAA0040	NM_001162894.2		c.-384+5568C>G		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.-384+5348C>G		intron	N/A	ENSP00000462172.1
	KIAA0040	ENST00000444639.5	TSL:1	c.-384+5568C>G		intron	N/A	ENSP00000463734.1
	KIAA0040	ENST00000545251.6	TSL:1	c.-310+5348C>G		intron	N/A	ENSP00000464040.1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74409 AN: 151890 Hom.: 18770 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.490 AC: 74414 AN: 152006 Hom.: 18763 Cov.: 32 AF XY: 0.490 AC XY: 36402 AN XY: 74292

African (AFR) AF: 0.383 AC: 15880 AN: 41468

American (AMR) AF: 0.407 AC: 6217 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1494 AN: 3468

East Asian (EAS) AF: 0.425 AC: 2194 AN: 5160

South Asian (SAS) AF: 0.524 AC: 2520 AN: 4806

European-Finnish (FIN) AF: 0.601 AC: 6337 AN: 10550

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38187 AN: 67962

Other (OTH) AF: 0.489 AC: 1032 AN: 2110

Alfa AF: 0.416 Hom.: 1306

Bravo AF: 0.465

Asia WGS AF: 0.464 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		0.73
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: rs3766685; hg19: chr1-175156428;