1-57010704-G-A

Variant names:

• chr1-57010704-G-A
• rs141647150
• NM_001365792.1:c.1659C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001365792.1(DAB1):​c.1659C>T​(p.Ala553Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,573,906 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A553A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (39 hom.)
• Consequence: DAB1 NM_001365792.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.04
• Publications: 2 publications found

Genes affected

DAB1 (HGNC:2661): (DAB adaptor protein 1) The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. [provided by RefSeq, Jan 2017]

DAB1 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 37

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

LOC112267900 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 1-57010704-G-A is Benign according to our data. Variant chr1-57010704-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 780002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.04 with no splicing effect.
• BS2: High AC in GnomAd4 at 719 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365792.1. 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
	DAB1	NM_001365792.1	MANE Select	c.1659C>T	p.Ala553Ala	synonymous	Exon 14 of 15	NP_001352721.1	O75553-6
	DAB1	NM_001353983.2		c.1659C>T	p.Ala553Ala	synonymous	Exon 14 of 15	NP_001340912.1	O75553-6
	DAB1	NM_001353985.2		c.1659C>T	p.Ala553Ala	synonymous	Exon 14 of 15	NP_001340914.1	O75553-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000371236.7	TSL:5 MANE Select	c.1659C>T	p.Ala553Ala	synonymous	Exon 14 of 15	ENSP00000360280.1	O75553-6
	DAB1	ENST00000420954.6	TSL:1	c.1653C>T	p.Ala551Ala	synonymous	Exon 13 of 14	ENSP00000395296.2	O75553-5
	DAB1	ENST00000371231.5	TSL:5	c.1758C>T	p.Ala586Ala	synonymous	Exon 15 of 15	ENSP00000360275.1	O75553-1

Frequencies

GnomAD3 genomes AF: 0.00473 AC: 720 AN: 152088 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00623

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.00546 AC: 1296 AN: 237194 AF XY: 0.00548

Gnomad AFR exome AF: 0.000965

Gnomad AMR exome AF: 0.00549

Gnomad ASJ exome AF: 0.0299

Gnomad EAS exome AF: 0.0000585

Gnomad FIN exome AF: 0.000516

Gnomad NFE exome AF: 0.00650

Gnomad OTH exome AF: 0.00703

GnomAD4 exome AF: 0.00561 AC: 7975 AN: 1421700 Hom.: 39 Cov.: 30 AF XY: 0.00561 AC XY: 3946 AN XY: 703920

African (AFR) AF: 0.00149 AC: 48 AN: 32108

American (AMR) AF: 0.00647 AC: 266 AN: 41124

Ashkenazi Jewish (ASJ) AF: 0.0289 AC: 719 AN: 24870

East Asian (EAS) AF: 0.0000777 AC: 3 AN: 38600

South Asian (SAS) AF: 0.00229 AC: 184 AN: 80514

European-Finnish (FIN) AF: 0.000704 AC: 37 AN: 52528

Middle Eastern (MID) AF: 0.00808 AC: 45 AN: 5570

European-Non Finnish (NFE) AF: 0.00579 AC: 6296 AN: 1088060

Other (OTH) AF: 0.00646 AC: 377 AN: 58326

GnomAD4 genome AF: 0.00472 AC: 719 AN: 152206 Hom.: 4 Cov.: 32 AF XY: 0.00446 AC XY: 332 AN XY: 74416

African (AFR) AF: 0.00152 AC: 63 AN: 41538

American (AMR) AF: 0.00615 AC: 94 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4824

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00629 AC: 428 AN: 67998

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00649 Hom.: 5

Bravo AF: 0.00541

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs141647150; hg19: chr1-57476377;