rs12745968

Variant names:

• chr1-92936280-A-G
• rs12745968
• NM_001006605.5:c.54+25096T>C

Variant summary

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

The NM_001006605.5(DIPK1A):​c.54+25096T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,070 control chromosomes in the GnomAD database, including 9,747 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 0.35 (9747 hom., cov: 31)
• Consequence: DIPK1A NM_001006605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 27 publications found

Genes affected

DIPK1A (HGNC:32213): (divergent protein kinase domain 1A) This gene encodes a member of the FAM69 family of cysteine-rich type II transmembrane proteins. These proteins localize to the endoplasmic reticulum but their specific functions are unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK1A	NM_001006605.5	c.54+25096T>C		intron_variant	Intron 1 of 4	ENST00000370310.5	NP_001006606.2
DIPK1A	NM_001252269.2	c.54+25096T>C		intron_variant	Intron 1 of 3		NP_001239198.1
DIPK1A	NM_001252270.2	c.54+25096T>C		intron_variant	Intron 1 of 3		NP_001239199.1
DIPK1A	NM_001252273.2	c.54+25096T>C		intron_variant	Intron 1 of 4		NP_001239202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIPK1A	ENST00000370310.5	c.54+25096T>C		intron_variant	Intron 1 of 4	2	NM_001006605.5	ENSP00000359333.4
DIPK1A	ENST00000615519.4	c.54+25096T>C		intron_variant	Intron 1 of 4	1		ENSP00000483279.1
DIPK1A	ENST00000613902.4	c.54+25096T>C		intron_variant	Intron 1 of 3	4		ENSP00000484866.1
DIPK1A	ENST00000616709.4	c.54+25096T>C		intron_variant	Intron 1 of 3	3		ENSP00000482718.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53119 AN: 151952 Hom.: 9736 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.350 AC: 53172 AN: 152070 Hom.: 9747 Cov.: 31 AF XY: 0.345 AC XY: 25666 AN XY: 74334

African (AFR) AF: 0.384 AC: 15937 AN: 41456

American (AMR) AF: 0.327 AC: 4996 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 828 AN: 3464

East Asian (EAS) AF: 0.0548 AC: 284 AN: 5186

South Asian (SAS) AF: 0.193 AC: 933 AN: 4824

European-Finnish (FIN) AF: 0.383 AC: 4050 AN: 10564

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24944 AN: 67970

Other (OTH) AF: 0.362 AC: 765 AN: 2112

Alfa AF: 0.353 Hom.: 29402

Bravo AF: 0.347

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.080
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: rs12745968; hg19: chr1-93401837;