NM_014656.3:c.-309-4446A>G

Variant names:

• chr1-175171183-T-C
• rs12136973
• NM_014656.3:c.-309-4446A>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.-309-4446A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,200 control chromosomes in the GnomAD database, including 4,932 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 (4932 hom., cov: 32)
• Consequence: KIAA0040 NM_014656.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.391 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.-309-4446A>G		intron	N/A	NP_055471.2
	KIAA0040	NM_001162893.2		c.-309-4446A>G		intron	N/A	NP_001156365.1
	KIAA0040	NM_001162894.2		c.-309-4446A>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.-309-4446A>G		intron	N/A	ENSP00000462172.1
	KIAA0040	ENST00000444639.5	TSL:1	c.-309-4446A>G		intron	N/A	ENSP00000463734.1
	KIAA0040	ENST00000545251.6	TSL:1	c.-309-4446A>G		intron	N/A	ENSP00000464040.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34070 AN: 152082 Hom.: 4924 Cov.: 32

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.224 AC: 34083 AN: 152200 Hom.: 4932 Cov.: 32 AF XY: 0.226 AC XY: 16794 AN XY: 74406

African (AFR) AF: 0.0525 AC: 2183 AN: 41552

American (AMR) AF: 0.399 AC: 6106 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1221 AN: 3472

East Asian (EAS) AF: 0.314 AC: 1626 AN: 5178

South Asian (SAS) AF: 0.308 AC: 1488 AN: 4826

European-Finnish (FIN) AF: 0.184 AC: 1944 AN: 10592

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.271 AC: 18420 AN: 67968

Other (OTH) AF: 0.269 AC: 570 AN: 2116

Alfa AF: 0.264 Hom.: 2961

Bravo AF: 0.236

Asia WGS AF: 0.285 AC: 990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.25
PhyloP100		-0.57
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: rs12136973; hg19: chr1-175140319;