2-64993776-T-C

Position:

• chr2-64993776-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003038.5(SLC1A4):​c.527+3606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,998 control chromosomes in the GnomAD database, including 21,031 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 0.51 (21031 hom., cov: 32)
• Consequence: SLC1A4 NM_003038.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

Genes affected

SLC1A4 (HGNC:10942): (solute carrier family 1 member 4) The protein encoded by this gene is a sodium-dependent neutral amino acid transporter for alanine, serine, cysteine, and threonine. Defects in this gene have been associated with developmental delay, microcephaly, and intellectual disability. [provided by RefSeq, Jan 2017]

LINC02245 (HGNC:53134): (long intergenic non-protein coding RNA 2245)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A4	NM_003038.5	c.527+3606T>C		intron_variant		ENST00000234256.4
SLC1A4	NM_001193493.2	c.-134+5156T>C		intron_variant
SLC1A4	NM_001348406.2	c.-134+5156T>C		intron_variant
SLC1A4	NM_001348407.2	c.-134+5222T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A4	ENST00000234256.4	c.527+3606T>C		intron_variant		1	NM_003038.5	P1
LINC02245	ENST00000653778.1	n.513+54178A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77787 AN: 151880 Hom.: 21011 Cov.: 32

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.515

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.512 AC: 77848 AN: 151998 Hom.: 21031 Cov.: 32 AF XY: 0.512 AC XY: 38022 AN XY: 74302

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.515

Alfa AF: 0.399 Hom.: 5031

Bravo AF: 0.537

Asia WGS AF: 0.557 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs2160387; hg19: chr2-65220910;