rs41272438

Variant names:

• chr8-60801631-A-T
• rs41272438
• NM_017780.4:c.2442+38A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-60801631-A-T
• chr8-60801631-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017780.4(CHD7):​c.2442+38A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,320,496 control chromosomes in the GnomAD database, including 755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (63 hom., cov: 32)
  • Exomes 𝑓: 0.032 (692 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.543
• Publications: 2 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Broad Center for Mendelian Genomics, 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-60801631-A-T is Benign according to our data. Variant chr8-60801631-A-T is described in ClinVar as Benign. ClinVar VariationId is 260895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0246 (3752/152298) while in subpopulation NFE AF = 0.0345 (2350/68024). AF 95% confidence interval is 0.0334. There are 63 homozygotes in GnomAd4. There are 1871 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 63 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	NM_017780.4	MANE Select	c.2442+38A>T		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1716+20581A>T		intron	N/A	NP_001303619.1	Q9P2D1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	ENST00000423902.7	TSL:5 MANE Select	c.2442+38A>T		intron	N/A	ENSP00000392028.1	Q9P2D1-1
	CHD7	ENST00000524602.5	TSL:1	c.1716+20581A>T		intron	N/A	ENSP00000437061.1	Q9P2D1-4
	CHD7	ENST00000933299.1		c.2442+38A>T		intron	N/A	ENSP00000603358.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3753 AN: 152180 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.00589

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0631

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.0258 AC: 4158 AN: 160876 AF XY: 0.0249

Gnomad AFR exome AF: 0.00441

Gnomad AMR exome AF: 0.0119

Gnomad ASJ exome AF: 0.0314

Gnomad EAS exome AF: 0.0000881

Gnomad FIN exome AF: 0.0585

Gnomad NFE exome AF: 0.0356

Gnomad OTH exome AF: 0.0287

GnomAD4 exome AF: 0.0325 AC: 37951 AN: 1168198 Hom.: 692 Cov.: 16 AF XY: 0.0317 AC XY: 18590 AN XY: 587024

African (AFR) AF: 0.00467 AC: 127 AN: 27212

American (AMR) AF: 0.0127 AC: 449 AN: 35278

Ashkenazi Jewish (ASJ) AF: 0.0298 AC: 703 AN: 23556

East Asian (EAS) AF: 0.0000282 AC: 1 AN: 35414

South Asian (SAS) AF: 0.00636 AC: 466 AN: 73320

European-Finnish (FIN) AF: 0.0577 AC: 2859 AN: 49588

Middle Eastern (MID) AF: 0.0183 AC: 95 AN: 5204

European-Non Finnish (NFE) AF: 0.0366 AC: 31805 AN: 868104

Other (OTH) AF: 0.0286 AC: 1446 AN: 50522

GnomAD4 genome AF: 0.0246 AC: 3752 AN: 152298 Hom.: 63 Cov.: 32 AF XY: 0.0251 AC XY: 1871 AN XY: 74460

African (AFR) AF: 0.00587 AC: 244 AN: 41570

American (AMR) AF: 0.0155 AC: 237 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4828

European-Finnish (FIN) AF: 0.0631 AC: 669 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0345 AC: 2350 AN: 68024

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0222 Hom.: 14

Bravo AF: 0.0205

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.61
DANN	Benign	0.49
PhyloP100		-0.54
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41272438;

hg19: chr8-61714190;