rs8192559

chr5-135535223-G-Achr5-135535223-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006161.3(NEUROG1):c.468C>T(p.Pro156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,612,210 control chromosomes in the GnomAD database, including 6,444 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 0.067 (512 hom., cov: 33)
  • Exomes 𝑓: 0.085 (5932 hom.)
• Consequence: NEUROG1 NM_006161.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.762

Genes affected

NEUROG1 (HGNC:7764): (neurogenin 1) Enables E-box binding activity and protein homodimerization activity. Involved in several processes, including animal organ morphogenesis; cranial nerve development; and hard palate morphogenesis. Predicted to be located in neuronal cell body. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.762 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.096 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEUROG1	NM_006161.3	c.468C>T	p.Pro156=	synonymous_variant	1/1	ENST00000314744.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEUROG1	ENST00000314744.6	c.468C>T	p.Pro156=	synonymous_variant	1/1		NM_006161.3	P1
	ENST00000698884.1	n.496+48454G>A		intron_variant, non_coding_transcript_variant
SLC25A48	ENST00000698885.1	n.364+25467G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10183 AN: 152140 Hom.: 513 Cov.: 33

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.0559

GnomAD3 exomes AF: 0.0689 AC: 16783 AN: 243628 Hom.: 752 AF XY: 0.0680 AC XY: 9040 AN XY: 133014

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.0720

Gnomad ASJ exome AF: 0.0541

Gnomad EAS exome AF: 0.000277

Gnomad SAS exome AF: 0.0180

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.0951

Gnomad OTH exome AF: 0.0747

GnomAD4 exome AF: 0.0852 AC: 124367 AN: 1459960 Hom.: 5932 Cov.: 32 AF XY: 0.0833 AC XY: 60531 AN XY: 726322

Gnomad4 AFR exome AF: 0.0137

Gnomad4 AMR exome AF: 0.0722

Gnomad4 ASJ exome AF: 0.0547

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.0182

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.0970

Gnomad4 OTH exome AF: 0.0724

GnomAD4 genome AF: 0.0669 AC: 10178 AN: 152250 Hom.: 512 Cov.: 33 AF XY: 0.0654 AC XY: 4866 AN XY: 74434

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0890

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.0980

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0693 Hom.: 117

Bravo AF: 0.0629

Asia WGS AF: 0.0130 AC: 45 AN: 3472

EpiCase AF: 0.0858

EpiControl AF: 0.0887

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	8.6
Dann	Benign	0.89

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: rs8192559; hg19: chr5-134870913; COSMIC: COSV59083234;