4-143336967-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002039.4(GAB1):c.-222C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00921 in 483,308 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (137 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (32 hom.)
• Consequence: GAB1 NM_002039.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.43

Genes affected

GAB1 (HGNC:4066): (GRB2 associated binding protein 1) The protein encoded by this gene is a member of the IRS1-like multisubstrate docking protein family. It is an important mediator of branching tubulogenesis and plays a central role in cellular growth response, transformation and apoptosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

LOC124900789 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 4-143336967-C-T is Benign according to our data. Variant chr4-143336967-C-T is described in ClinVar as [Benign]. Clinvar id is 1267291.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAB1	NM_002039.4	c.-222C>T		5_prime_UTR_variant	1/10	ENST00000262994.9
LOC124900789	XR_007058287.1	n.224G>A		non_coding_transcript_exon_variant	1/1
GAB1	NM_207123.3	c.-222C>T		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAB1	ENST00000262994.9	c.-222C>T		5_prime_UTR_variant	1/10	1	NM_002039.4	A1
GAB1	ENST00000262995.9	c.-222C>T		5_prime_UTR_variant	1/11	1		P3

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3664 AN: 151720 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00866

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00237 AC: 787 AN: 331474 Hom.: 32 Cov.: 3 AF XY: 0.00204 AC XY: 354 AN XY: 173530

Gnomad4 AFR exome AF: 0.0793

Gnomad4 AMR exome AF: 0.00605

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000191

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000146

Gnomad4 OTH exome AF: 0.00611

GnomAD4 genome AF: 0.0241 AC: 3664 AN: 151834 Hom.: 137 Cov.: 32 AF XY: 0.0239 AC XY: 1771 AN XY: 74236

Gnomad4 AFR AF: 0.0841

Gnomad4 AMR AF: 0.00864

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0301 Hom.: 13

Bravo AF: 0.0277

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	12
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs28989190; hg19: chr4-144258120;