rs2252508

Variant names:

• chr1-153941294-A-C
• rs2252508
• NM_014856.3:c.1123-5T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-153941294-A-C
• chr1-153941294-A-G
• chr1-153941294-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014856.3(DENND4B):​c.1123-5T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DENND4B NM_014856.3 splice_region, intron
• Scores: Splicing: ADA: 0.0002149
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

Genes affected

DENND4B (HGNC:29044): (DENN domain containing 4B) Enables guanyl-nucleotide exchange factor activity. Involved in regulation of Rab protein signal transduction. Located in Golgi apparatus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND4B	NM_014856.3	c.1123-5T>G		splice_region_variant, intron_variant	Intron 7 of 27	ENST00000361217.9	NP_055671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND4B	ENST00000361217.9	c.1123-5T>G		splice_region_variant, intron_variant	Intron 7 of 27	1	NM_014856.3	ENSP00000354597.4
DENND4B	ENST00000368646.6	c.1156-5T>G		splice_region_variant, intron_variant	Intron 7 of 21	5		ENSP00000357635.2
DENND4B	ENST00000483561.2	n.444-5T>G		splice_region_variant, intron_variant	Intron 2 of 2	4
DENND4B	ENST00000494683.1	n.62-5T>G		splice_region_variant, intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00021
dbscSNV1_RF	Benign	0.056
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2252508; hg19: chr1-153913770;