rs2075209

Positions:

• chr2-65018989-G-A
• chr2-65018989-G-C

Variant summary

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

The NM_003038.5(SLC1A4):​c.1364+310G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,266 control chromosomes in the GnomAD database, including 2,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (2760 hom., cov: 33)
• Consequence: SLC1A4 NM_003038.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.05

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-65018989-G-A is Benign according to our data. Variant chr2-65018989-G-A is described in ClinVar as [Benign]. Clinvar id is 1294955.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A4	NM_003038.5	c.1364+310G>A		intron_variant		ENST00000234256.4	NP_003029.2
SLC1A4	NM_001193493.2	c.470+310G>A		intron_variant			NP_001180422.1
SLC1A4	NM_001348406.2	c.704+310G>A		intron_variant			NP_001335335.1
SLC1A4	NM_001348407.2	c.704+310G>A		intron_variant			NP_001335336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A4	ENST00000234256.4	c.1364+310G>A		intron_variant		1	NM_003038.5	ENSP00000234256	P1
LINC02245	ENST00000653778.1	n.513+28965C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28238 AN: 152148 Hom.: 2756 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.186 AC: 28259 AN: 152266 Hom.: 2760 Cov.: 33 AF XY: 0.185 AC XY: 13766 AN XY: 74432

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.218

Alfa AF: 0.187 Hom.: 5707

Bravo AF: 0.186

Asia WGS AF: 0.310 AC: 1078 AN: 3478

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.43

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: rs2075209; hg19: chr2-65246123;