2-64989514-G-C

Position:

• chr2-64989514-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003038.5(SLC1A4):​c.-130G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 781,892 control chromosomes in the GnomAD database, including 9,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1747 hom., cov: 33)
  • Exomes 𝑓: 0.16 (7947 hom.)
• Consequence: SLC1A4 NM_003038.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.324

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-64989514-G-C is Benign according to our data. Variant chr2-64989514-G-C is described in ClinVar as [Benign]. Clinvar id is 1274353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A4	NM_003038.5	c.-130G>C		5_prime_UTR_variant	1/8	ENST00000234256.4
SLC1A4	NM_001193493.2	c.-134+894G>C		intron_variant
SLC1A4	NM_001348406.2	c.-134+894G>C		intron_variant
SLC1A4	NM_001348407.2	c.-134+960G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A4	ENST00000234256.4	c.-130G>C		5_prime_UTR_variant	1/8	1	NM_003038.5	P1
LINC02245	ENST00000653778.1	n.513+58440C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23071 AN: 152068 Hom.: 1742 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.155 AC: 97713 AN: 629710 Hom.: 7947 Cov.: 9 AF XY: 0.154 AC XY: 48085 AN XY: 312900

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.152 AC: 23093 AN: 152182 Hom.: 1747 Cov.: 33 AF XY: 0.152 AC XY: 11347 AN XY: 74410

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.159

Alfa AF: 0.140 Hom.: 193

Bravo AF: 0.154

Asia WGS AF: 0.182 AC: 633 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.8
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7609068; hg19: chr2-65216648; COSMIC: COSV52235357;