7-74210285-C-T

Variant names:

• chr7-74210285-C-T
• rs7810996
• NM_032464.3:c.-219+197C>T

Variant summary

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

The NM_032464.3(LAT2):​c.-219+197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,112 control chromosomes in the GnomAD database, including 6,357 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 0.29 (6357 hom., cov: 32)
• Consequence: LAT2 NM_032464.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 10 publications found

Genes affected

LAT2 (HGNC:12749): (linker for activation of T cells family member 2) This gene is one of the contiguous genes at 7q11.23 commonly deleted in Williams syndrome, a multisystem developmental disorder. This gene consists of at least 14 exons, and its alternative splicing generates 3 transcript variants, all encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAT2	NM_032464.3	c.-219+197C>T		intron_variant	Intron 1 of 13	ENST00000460943.6	NP_115853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAT2	ENST00000460943.6	c.-219+197C>T		intron_variant	Intron 1 of 13	1	NM_032464.3	ENSP00000420494.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43522 AN: 151994 Hom.: 6354 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.286 AC: 43529 AN: 152112 Hom.: 6357 Cov.: 32 AF XY: 0.283 AC XY: 21018 AN XY: 74356

African (AFR) AF: 0.295 AC: 12230 AN: 41496

American (AMR) AF: 0.298 AC: 4549 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 997 AN: 3470

East Asian (EAS) AF: 0.113 AC: 582 AN: 5172

South Asian (SAS) AF: 0.282 AC: 1360 AN: 4822

European-Finnish (FIN) AF: 0.237 AC: 2512 AN: 10604

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20212 AN: 67952

Other (OTH) AF: 0.281 AC: 595 AN: 2116

Alfa AF: 0.288 Hom.: 23575

Bravo AF: 0.290

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.29
PhyloP100		-1.1
PromoterAI		-0.00010	Neutral
Mutation Taster		=100/0	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: rs7810996; hg19: chr7-73624615;