chr7-44044769-C-T

Variant names:

• chr7-44044769-C-T
• rs771491870
• NM_001014436.3:c.32C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001014436.3(DBNL):​c.32C>T​(p.Ala11Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000398 in 1,507,368 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: DBNL NM_001014436.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.48
• 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]

ENSG00000288746 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40439606).

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.32C>T	p.Ala11Val	missense	Exon 1 of 13	NP_001014436.1	Q9UJU6-1
	DBNL	NM_001122956.2		c.32C>T	p.Ala11Val	missense	Exon 1 of 13	NP_001116428.1	Q9UJU6-3
	DBNL	NM_001362723.2		c.32C>T	p.Ala11Val	missense	Exon 1 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.32C>T	p.Ala11Val	missense	Exon 1 of 13	ENSP00000411701.1	Q9UJU6-1
	DBNL	ENST00000494774.5	TSL:1	c.32C>T	p.Ala11Val	missense	Exon 1 of 13	ENSP00000419992.1	Q9UJU6-2
	DBNL	ENST00000967647.1		c.32C>T	p.Ala11Val	missense	Exon 1 of 14	ENSP00000637706.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000369 AC: 5 AN: 1355244 Hom.: 0 Cov.: 33 AF XY: 0.00000299 AC XY: 2 AN XY: 668548

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27154

American (AMR) AF: 0.0000644 AC: 2 AN: 31044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23722

East Asian (EAS) AF: 0.00 AC: 0 AN: 30882

South Asian (SAS) AF: 0.00 AC: 0 AN: 76580

European-Finnish (FIN) AF: 0.0000230 AC: 1 AN: 43406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1060812

Other (OTH) AF: 0.00 AC: 0 AN: 56066

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000299538), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74284

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

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	Uncertain	0.34
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.5
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.17
Sift	Benign	0.068	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.39
MutPred		0.38		Loss of disorder (P = 0.0769)
MVP		0.73
MPC		0.00027
ClinPred		0.99	D
GERP RS		5.0
PromoterAI		-0.0040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.43
gMVP		0.53
Mutation Taster		=32/68	disease causing

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: rs771491870; hg19: chr7-44084368;