chr1-57014875-G-T

Variant names:

• chr1-57014875-G-T
• rs183171115
• NM_001365792.1:c.1444+8C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001365792.1(DAB1):​c.1444+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000992 in 1,541,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: DAB1 NM_001365792.1 splice_region, intron
• Scores: Splicing: ADA: 0.00004121
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.255
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-57014875-G-T is Benign according to our data. Variant chr1-57014875-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 738808.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 78 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.1444+8C>A		splice_region intron	N/A	NP_001352721.1	O75553-6
	DAB1	NM_001353983.2		c.1444+8C>A		splice_region intron	N/A	NP_001340912.1	O75553-6
	DAB1	NM_001353985.2		c.1444+8C>A		splice_region intron	N/A	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.1444+8C>A		splice_region intron	N/A	ENSP00000360280.1	O75553-6
	DAB1	ENST00000420954.6	TSL:1	c.1438+8C>A		splice_region intron	N/A	ENSP00000395296.2	O75553-5
	DAB1	ENST00000371231.5	TSL:5	c.1543+8C>A		splice_region intron	N/A	ENSP00000360275.1	O75553-1

Frequencies

GnomAD3 genomes AF: 0.000513 AC: 78 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000136 AC: 27 AN: 198908 AF XY: 0.000115

Gnomad AFR exome AF: 0.00115

Gnomad AMR exome AF: 0.000222

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000215

Gnomad OTH exome AF: 0.000214

GnomAD4 exome AF: 0.0000540 AC: 75 AN: 1389742 Hom.: 0 Cov.: 31 AF XY: 0.0000601 AC XY: 41 AN XY: 682298

African (AFR) AF: 0.00147 AC: 46 AN: 31396

American (AMR) AF: 0.000194 AC: 7 AN: 36004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21472

East Asian (EAS) AF: 0.00 AC: 0 AN: 38952

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 73880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5402

European-Non Finnish (NFE) AF: 0.00000744 AC: 8 AN: 1074568

Other (OTH) AF: 0.000227 AC: 13 AN: 57204

GnomAD4 genome AF: 0.000512 AC: 78 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74442

African (AFR) AF: 0.00159 AC: 66 AN: 41544

American (AMR) AF: 0.000720 AC: 11 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000329 Hom.: 0

Bravo AF: 0.000521

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.6
DANN	Benign	0.74
PhyloP100		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000041
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs183171115; hg19: chr1-57480548;