rs1483208

Variant names:

• chr8-60755339-G-A
• rs1483208
• NM_017780.4:c.1665+12242G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-60755339-G-A
• chr8-60755339-G-T

Variant summary

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

The NM_017780.4(CHD7):​c.1665+12242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,968 control chromosomes in the GnomAD database, including 24,895 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 0.52 (24895 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 5 publications found

Genes affected

CHD7 (HGNC:20626): (chromodomain helicase DNA binding protein 7) This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

CHD7 Gene-Disease associations (from GenCC):

• CHARGE syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Broad Center for Mendelian Genomics, ClinGen, G2P
• hypogonadotropic hypogonadism 5 with or without anosmia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.1665+12242G>A		intron_variant	Intron 2 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.1665+12242G>A		intron_variant	Intron 2 of 37	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79059 AN: 151850 Hom.: 24887 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.520 AC: 79080 AN: 151968 Hom.: 24895 Cov.: 32 AF XY: 0.529 AC XY: 39302 AN XY: 74284

African (AFR) AF: 0.143 AC: 5945 AN: 41502

American (AMR) AF: 0.618 AC: 9446 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2137 AN: 3470

East Asian (EAS) AF: 0.781 AC: 4039 AN: 5170

South Asian (SAS) AF: 0.729 AC: 3515 AN: 4824

European-Finnish (FIN) AF: 0.684 AC: 7173 AN: 10490

Middle Eastern (MID) AF: 0.458 AC: 132 AN: 288

European-Non Finnish (NFE) AF: 0.663 AC: 45038 AN: 67924

Other (OTH) AF: 0.534 AC: 1126 AN: 2108

Alfa AF: 0.576 Hom.: 3442

Bravo AF: 0.497

Asia WGS AF: 0.678 AC: 2341 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.025
DANN	Benign	0.48
PhyloP100		-2.5
Mutation Taster		=100/0	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: rs1483208; hg19: chr8-61667898;