19-44703545-C-T

Variant names:

• chr19-44703545-C-T
• rs73568059
• NM_001039213.4:c.234C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001039213.4(CEACAM16):​c.234C>T​(p.Gly78Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,613,374 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: CEACAM16 NM_001039213.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.18
• Publications: 0 publications found

Genes affected

CEACAM16 (HGNC:31948): (CEA cell adhesion molecule 16, tectorial membrane component) The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 19-44703545-C-T is Benign according to our data. Variant chr19-44703545-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 504817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.18 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00286 (435/152314) while in subpopulation AFR AF = 0.0102 (424/41582). AF 95% confidence interval is 0.0094. There are 4 homozygotes in GnomAd4. There are 207 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039213.4. 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
	CEACAM16	NM_001039213.4	MANE Select	c.234C>T	p.Gly78Gly	synonymous	Exon 3 of 7	NP_001034302.2
	CEACAM16-AS1	NR_186815.1		n.348-4368G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	ENST00000587331.7	TSL:1 MANE Select	c.234C>T	p.Gly78Gly	synonymous	Exon 3 of 7	ENSP00000466561.1
	CEACAM16	ENST00000405314.2	TSL:5	c.234C>T	p.Gly78Gly	synonymous	Exon 2 of 6	ENSP00000385576.1
	CEACAM16-AS1	ENST00000590796.1	TSL:5	n.315-4368G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00286 AC: 436 AN: 152196 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000783 AC: 192 AN: 245166 AF XY: 0.000681

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000911

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000272 AC: 398 AN: 1461060 Hom.: 0 Cov.: 32 AF XY: 0.000244 AC XY: 177 AN XY: 726834

African (AFR) AF: 0.0104 AC: 349 AN: 33478

American (AMR) AF: 0.000492 AC: 22 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52970

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111800

Other (OTH) AF: 0.000365 AC: 22 AN: 60350

GnomAD4 genome AF: 0.00286 AC: 435 AN: 152314 Hom.: 4 Cov.: 32 AF XY: 0.00278 AC XY: 207 AN XY: 74488

African (AFR) AF: 0.0102 AC: 424 AN: 41582

American (AMR) AF: 0.000392 AC: 6 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.000666 Hom.: 0

Bravo AF: 0.00354

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Autosomal dominant nonsyndromic hearing loss 4B;C5193079:Hearing loss, autosomal recessive 113 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.32
DANN	Benign	0.56
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism

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: rs73568059; hg19: chr19-45206815;