chr7-44056874-T-C

Variant names:

• chr7-44056874-T-C
• rs2096137379
• NM_001014436.3:c.445T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001014436.3(DBNL):​c.445T>C​(p.Phe149Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: DBNL NM_001014436.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• Publications: 0 publications found

Genes affected

DBNL (HGNC:2696): (drebrin like) Enables cadherin binding activity. Predicted to be involved in several processes, including Rac protein signal transduction; nervous system development; and podosome assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26149648).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014436.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBNL	NM_001014436.3	MANE Select	c.445T>C	p.Phe149Leu	missense	Exon 5 of 13	NP_001014436.1	Q9UJU6-1
	DBNL	NM_001122956.2		c.445T>C	p.Phe149Leu	missense	Exon 5 of 13	NP_001116428.1	Q9UJU6-3
	DBNL	NM_001362723.2		c.445T>C	p.Phe149Leu	missense	Exon 5 of 13	NP_001349652.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBNL	ENST00000448521.6	TSL:1 MANE Select	c.445T>C	p.Phe149Leu	missense	Exon 5 of 13	ENSP00000411701.1	Q9UJU6-1
	DBNL	ENST00000494774.5	TSL:1	c.445T>C	p.Phe149Leu	missense	Exon 5 of 13	ENSP00000419992.1	Q9UJU6-2
	DBNL	ENST00000497184.5	TSL:1	n.2252T>C		non_coding_transcript_exon	Exon 3 of 10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461774 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.11
Sift	Benign	0.10	T
Sift4G	Benign	0.63	T
Polyphen		0.95	P
Vest4		0.36
MutPred		0.26		Gain of MoRF binding (P = 0.1828)
MVP		0.71
MPC		1.9
ClinPred		0.94	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.41
Mutation Taster		=64/36	polymorphism

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: rs2096137379; hg19: chr7-44096473;