2-64989955-G-C

Variant names:

• chr2-64989955-G-C
• rs7559202
• NM_003038.5:c.312G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003038.5(SLC1A4):​c.312G>C​(p.Ser104Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,574,396 control chromosomes in the GnomAD database, including 18,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1773 hom., cov: 33)
  • Exomes 𝑓: 0.15 (16272 hom.)
• Consequence: SLC1A4 NM_003038.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0860
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 2-64989955-G-C is Benign according to our data. Variant chr2-64989955-G-C is described in ClinVar as Benign. ClinVar VariationId is 1170224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.086 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003038.5. 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
	SLC1A4	NM_003038.5	MANE Select	c.312G>C	p.Ser104Ser	synonymous	Exon 1 of 8	NP_003029.2
	SLC1A4	NM_001348406.2		c.-134+1335G>C		intron	N/A	NP_001335335.1
	SLC1A4	NM_001348407.2		c.-134+1401G>C		intron	N/A	NP_001335336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A4	ENST00000234256.4	TSL:1 MANE Select	c.312G>C	p.Ser104Ser	synonymous	Exon 1 of 8	ENSP00000234256.3
	LINC02245	ENST00000771819.1		n.313C>G		non_coding_transcript_exon	Exon 1 of 3
	SLC1A4	ENST00000531327.5	TSL:2	c.-134+1335G>C		intron	N/A	ENSP00000431942.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23126 AN: 152142 Hom.: 1768 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.158

GnomAD2 exomes AF: 0.149 AC: 27687 AN: 185762 AF XY: 0.150

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.206

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.150 AC: 213249 AN: 1422136 Hom.: 16272 Cov.: 33 AF XY: 0.149 AC XY: 104961 AN XY: 704030

African (AFR) AF: 0.170 AC: 5570 AN: 32704

American (AMR) AF: 0.129 AC: 5098 AN: 39602

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4176 AN: 25504

East Asian (EAS) AF: 0.222 AC: 8327 AN: 37560

South Asian (SAS) AF: 0.141 AC: 11545 AN: 81714

European-Finnish (FIN) AF: 0.142 AC: 6853 AN: 48410

Middle Eastern (MID) AF: 0.122 AC: 669 AN: 5478

European-Non Finnish (NFE) AF: 0.149 AC: 162271 AN: 1092372

Other (OTH) AF: 0.149 AC: 8740 AN: 58792

GnomAD4 genome AF: 0.152 AC: 23148 AN: 152260 Hom.: 1773 Cov.: 33 AF XY: 0.153 AC XY: 11375 AN XY: 74462

African (AFR) AF: 0.170 AC: 7074 AN: 41560

American (AMR) AF: 0.127 AC: 1937 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 602 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1159 AN: 5176

South Asian (SAS) AF: 0.149 AC: 722 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1399 AN: 10618

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9682 AN: 67988

Other (OTH) AF: 0.158 AC: 333 AN: 2110

Alfa AF: 0.140 Hom.: 516

Bravo AF: 0.154

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.0
DANN	Benign	0.87
PhyloP100		0.086
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7559202; hg19: chr2-65217089; COSMIC: COSV52234401; COSMIC: COSV52234401;