7-151058086-T-G

Variant names:

• chr7-151058086-T-G
• rs2069443
• ENST00000483786.5:c.-64+805T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000483786.5(SLC4A2):​c.-64+805T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 567,404 control chromosomes in the GnomAD database, including 25,478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8193 hom., cov: 33)
  • Exomes 𝑓: 0.28 (17285 hom.)
• Consequence: SLC4A2 ENST00000483786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 25 publications found

Genes affected

SLC4A2 (HGNC:11028): (solute carrier family 4 member 2) This gene encodes a member of the anion exchanger family of membrane transport proteins. The encoded protein regulates intracellular pH, biliary bicarbonate secretion, and chloride uptake. Reduced expression of this gene may be associated with primary biliary cirrhosis (PBC) in human patients, while differential expression of this gene may be associated with malignant hepatocellular carcinoma, colon and gastric cancers. [provided by RefSeq, Nov 2016]

CDK5 (HGNC:1774): (cyclin dependent kinase 5) This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins. Unlike other members of the family, the protein encoded by this gene does not directly control cell cycle regulation. Instead the protein, which is predominantly expressed at high levels in mammalian postmitotic central nervous system neurons, functions in diverse processes such as synaptic plasticity and neuronal migration through phosphorylation of proteins required for cytoskeletal organization, endocytosis and exocytosis, and apoptosis. In humans, an allelic variant of the gene that results in undetectable levels of the protein has been associated with lethal autosomal recessive lissencephaly-7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

CDK5 Gene-Disease associations (from GenCC):

• lissencephaly 7 with cerebellar hypoplasia

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000483786.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5	NM_004935.4	MANE Select	c.-238A>C		upstream_gene	N/A	NP_004926.1
	SLC4A2	NM_001199692.3		c.-1166T>G		upstream_gene	N/A	NP_001186621.1
	CDK5	NM_001164410.3		c.-238A>C		upstream_gene	N/A	NP_001157882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	ENST00000483786.5	TSL:4	c.-64+805T>G		intron	N/A	ENSP00000417808.1
	CDK5	ENST00000485972.6	TSL:1 MANE Select	c.-238A>C		upstream_gene	N/A	ENSP00000419782.1
	SLC4A2	ENST00000485713.6	TSL:1	c.-1166T>G		upstream_gene	N/A	ENSP00000419412.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48695 AN: 152086 Hom.: 8180 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.281 AC: 116840 AN: 415200 Hom.: 17285 Cov.: 3 AF XY: 0.280 AC XY: 60895 AN XY: 217764

African (AFR) AF: 0.394 AC: 4266 AN: 10830

American (AMR) AF: 0.510 AC: 6954 AN: 13638

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 3949 AN: 12912

East Asian (EAS) AF: 0.305 AC: 8492 AN: 27834

South Asian (SAS) AF: 0.259 AC: 10469 AN: 40380

European-Finnish (FIN) AF: 0.295 AC: 8543 AN: 28924

Middle Eastern (MID) AF: 0.302 AC: 561 AN: 1856

European-Non Finnish (NFE) AF: 0.262 AC: 66610 AN: 254506

Other (OTH) AF: 0.288 AC: 6996 AN: 24320

GnomAD4 genome AF: 0.320 AC: 48736 AN: 152204 Hom.: 8193 Cov.: 33 AF XY: 0.323 AC XY: 24053 AN XY: 74406

African (AFR) AF: 0.388 AC: 16132 AN: 41532

American (AMR) AF: 0.424 AC: 6480 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1619 AN: 5166

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4820

European-Finnish (FIN) AF: 0.295 AC: 3126 AN: 10600

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.263 AC: 17863 AN: 67998

Other (OTH) AF: 0.309 AC: 653 AN: 2116

Alfa AF: 0.297 Hom.: 10626

Bravo AF: 0.341

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.1
DANN	Benign	0.55
PhyloP100		0.10
PromoterAI		-0.028	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2069443; hg19: chr7-150755173;