7-44044769-C-G

Variant names:

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

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>G​(p.Ala11Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000059 in 1,355,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: DBNL NM_001014436.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.2656477).

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>G	p.Ala11Gly	missense	Exon 1 of 13	NP_001014436.1	Q9UJU6-1
	DBNL	NM_001122956.2		c.32C>G	p.Ala11Gly	missense	Exon 1 of 13	NP_001116428.1	Q9UJU6-3
	DBNL	NM_001362723.2		c.32C>G	p.Ala11Gly	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>G	p.Ala11Gly	missense	Exon 1 of 13	ENSP00000411701.1	Q9UJU6-1
	DBNL	ENST00000494774.5	TSL:1	c.32C>G	p.Ala11Gly	missense	Exon 1 of 13	ENSP00000419992.1	Q9UJU6-2
	DBNL	ENST00000967647.1		c.32C>G	p.Ala11Gly	missense	Exon 1 of 14	ENSP00000637706.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000268 AC: 3 AN: 111836 AF XY: 0.0000490

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000590 AC: 8 AN: 1355246 Hom.: 0 Cov.: 33 AF XY: 0.0000120 AC XY: 8 AN XY: 668548

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

American (AMR) AF: 0.00 AC: 0 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: 0.000104 AC: 8 AN: 76580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43406

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1060814

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

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000209 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.5
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.023	D
Sift4G	Benign	0.14	T
Polyphen		0.0050	B
Vest4		0.34
MutPred		0.45		Gain of disorder (P = 0.0777)
MVP		0.65
MPC		0.00027
ClinPred		0.50	T
GERP RS		5.0
PromoterAI		-0.045	Neutral
Varity_R		0.44
gMVP		0.32
Mutation Taster		=35/65	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;